research paper silver nanoparticles

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Int J Mol Sci

Silver Nanoparticles: Synthesis, Characterization, Properties, Applications, and Therapeutic Approaches

Xi-feng zhang.

1 College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China; moc.361@5649fxgnahz (X.-F.Z.); moc.621@l_ougihz (Z.-G.L.)

Zhi-Guo Liu

2 Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China; moc.621@724iewnehs

Sangiliyandi Gurunathan

3 Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 143-701, Korea

Recent advances in nanoscience and nanotechnology radically changed the way we diagnose, treat, and prevent various diseases in all aspects of human life. Silver nanoparticles (AgNPs) are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications. AgNPs play an important role in nanoscience and nanotechnology, particularly in nanomedicine. Although several noble metals have been used for various purposes, AgNPs have been focused on potential applications in cancer diagnosis and therapy. In this review, we discuss the synthesis of AgNPs using physical, chemical, and biological methods. We also discuss the properties of AgNPs and methods for their characterization. More importantly, we extensively discuss the multifunctional bio-applications of AgNPs; for example, as antibacterial, antifungal, antiviral, anti-inflammatory, anti-angiogenic, and anti-cancer agents, and the mechanism of the anti-cancer activity of AgNPs. In addition, we discuss therapeutic approaches and challenges for cancer therapy using AgNPs. Finally, we conclude by discussing the future perspective of AgNPs.

1. Introduction

Silver nanoparticles (AgNPs) are increasingly used in various fields, including medical, food, health care, consumer, and industrial purposes, due to their unique physical and chemical properties. These include optical, electrical, and thermal, high electrical conductivity, and biological properties [ 1 , 2 , 3 ]. Due to their peculiar properties, they have been used for several applications, including as antibacterial agents, in industrial, household, and healthcare-related products, in consumer products, medical device coatings, optical sensors, and cosmetics, in the pharmaceutical industry, the food industry, in diagnostics, orthopedics, drug delivery, as anticancer agents, and have ultimately enhanced the tumor-killing effects of anticancer drugs [ 4 ]. Recently, AgNPs have been frequently used in many textiles, keyboards, wound dressings, and biomedical devices [ 2 , 5 , 6 ]. Nanosized metallic particles are unique and can considerably change physical, chemical, and biological properties due to their surface-to-volume ratio; therefore, these nanoparticles have been exploited for various purposes [ 7 , 8 ]. In order to fulfill the requirement of AgNPs, various methods have been adopted for synthesis. Generally, conventional physical and chemical methods seem to be very expensive and hazardous [ 1 , 9 ]. Interestingly, biologically-prepared AgNPs show high yield, solubility, and high stability [ 1 ]. Among several synthetic methods for AgNPs, biological methods seem to be simple, rapid, non-toxic, dependable, and green approaches that can produce well-defined size and morphology under optimized conditions for translational research. In the end, a green chemistry approach for the synthesis of AgNPs shows much promise.

After synthesis, precise particle characterization is necessary, because the physicochemical properties of a particle could have a significant impact on their biological properties. In order to address the safety issue to use the full potential of any nano material in the purpose of human welfare, in nanomedicines, or in the health care industry, etc., it is necessary to characterize the prepared nanoparticles before application [ 10 , 11 ]. The characteristic feature of nanomaterials, such as size, shape, size distribution, surface area, shape, solubility, aggregation, etc. need to be evaluated before assessing toxicity or biocompatibility [ 12 ]. To evaluate the synthesized nanomaterials, many analytical techniques have been used, including ultraviolet visible spectroscopy (UV-vis spectroscopy), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), and so on [ 13 , 14 ].

The biological activity of AgNPs depends on factors including surface chemistry, size, size distribution, shape, particle morphology, particle composition, coating/capping, agglomeration, and dissolution rate, particle reactivity in solution, efficiency of ion release, and cell type, and the type of reducing agents used for the synthesis of AgNPs are a crucial factor for the determination of cytotoxicity [ 15 ]. The physicochemical properties of nanoparticles enhance the bioavailability of therapeutic agents after both systemic and local administration [ 16 , 17 ] and other hand it can affect cellular uptake, biological distribution, penetration into biological barriers, and resultant therapeutic effects [ 18 , 19 ]. Therefore, the development of AgNPs with controlled structures that are uniform in size, morphology, and functionality are essential for various biomedical applications [ 20 , 21 , 22 , 23 , 24 ].

Cancer is a complex, multifactorial disease which has the characteristic feature of the uncontrolled growth and spread of abnormal cells caused by several factors, including a combination of genetic, external, internal, and environmental factors [ 25 ], and it is treated by various treatments including chemotherapy, hormone therapy, surgery, radiation, immune therapy, and targeted therapy [ 25 ]. Therefore, the challenge is to identify effective, cost-effective, and sensitive lead molecules that have cell-targeted specificity and increase the sensitivity. Recently, AgNPs have been shown much interest because of their therapeutic applications in cancer as anticancer agents, in diagnostics, and in probing. Taken literature into consideration, in this review we focused on recent developments in synthesis, characterization, properties, and bio-applications mainly on the antibacterial, antifungal, antiviral, anti-inflammatory, anti-cancer and anti-angiogenic properties of AgNPs in a single platform. This review also emphasizes mechanism of anticancer activity, therapeutic approaches and the challenges and limitations of nanoparticles in cancer therapy. Finally, this review ends with conclusion and the future perspective of AgNPs.

2. Synthesis of AgNPs

2.1. synthesis of agnps using physical and chemical methods.

Generally, the synthesis of nanoparticles has been carried out using three different approaches, including physical, chemical, and biological methods. In physical methods, nanoparticles are prepared by evaporation-condensation using a tube furnace at atmospheric pressure [ 26 , 27 , 28 , 29 ]. Conventional physical methods including spark discharging and pyrolysis were used for the synthesis of AgNPs [ 30 , 31 ]. The advantages of physical methods are speed, radiation used as reducing agents, and no hazardous chemicals involved, but the downsides are low yield and high energy consumption, solvent contamination, and lack of uniform distribution [ 32 , 33 , 34 , 35 , 36 ].

Chemical methods use water or organic solvents to prepare the silver nanoparticles [ 37 , 38 ]. This process usually employs three main components, such as metal precursors, reducing agents, and stabilizing/capping agents. Basically, the reduction of silver salts involves two stages (1) nucleation; and (2) subsequent growth. In general, silver nanomaterials can be obtained by two methods, classified as “top-down” and “bottom-up” [ 39 ]. The “top-down” method is the mechanical grinding of bulk metals with subsequent stabilization using colloidal protecting agents [ 40 , 41 ]. The “bottom-up” methods include chemical reduction, electrochemical methods, and sono-decomposition. The major advantage of chemical methods is high yield, contrary to physical methods, which have low yield. The above-mentioned methods are extremely expensive. Additionally, the materials used for AgNPs synthesis, such as citrate, borohydride, thio-glycerol, and 2-mercaptoethanol are toxic and hazardous [ 41 ]. Apart from these disadvantages, the manufactured particles are not of expected purity, as their surfaces were found to be sedimented with chemicals. It is also very difficult to prepare AgNPs with a well-defined size, requiring a further step for the prevention of particle aggregation [ 42 ]. In addition, during the synthesis process, too many toxic and hazardous byproducts are excised out. Chemical methods make use of techniques such as cryochemical synthesis [ 43 ], laser ablation [ 44 ], lithography [ 45 ], electrochemical reduction [ 46 ], laser irradiation [ 47 ], sono-decomposition [ 48 ], thermal decomposition [ 49 ], and chemical reduction [ 50 ]. The advantage of the chemical synthesis of nanoparticles are the ease of production, low cost, and high yield; however, the use of chemical reducing agents are harmful to living organisms [ 13 ]. Recently, Abbasi et al. explained a detailed account of synthesis methods, properties, and bio-application of AgNPs [ 51 ].

2.2. Green Chemistry Approach for the Synthesis of AgNPs

To overcome the shortcomings of chemical methods, biological methods have emerged as viable options. Recently, biologically-mediated synthesis of nanoparticles have been shown to be simple, cost effective, dependable, and environmentally friendly approaches and much attention has been given to the high yield production of AgNPs of defined size using various biological systems including bacteria, fungi, plant extracts, and small biomolecules like vitamins and amino acids as an alternative method to chemical methods—not only for AgNPs, but also for the synthesis of several other nanoparticles, such as gold and graphene [ 9 , 52 , 53 , 54 , 55 , 56 ]. Bio-sorption of metals by Gram-negative and Gram-positive bacteria provided an indication for the synthesis of nanoparticles before the flourishing of this biological method; however, the synthesized nanomaterials were as aggregates not nanoparticles [ 57 ]. Several studies reported the synthesis of AgNPs using green, cost effective, and biocompatible methods without the use of toxic chemicals in biological methods. In this green chemistry approach, several bacteria, including Pseudomonas stutzeri AG259 [ 58 ], Lactobacillus strains [ 59 ], Bacillus licheniformis [ 55 ]; Escherichia coli ( E. coli ) [ 9 ], Brevibacterium casei [ 60 ], fungi including Fusarium oxysporum [ 61 ], Ganoderma neo-japonicum Imazeki [ 62 ], plant extracts such as Allophylus cobbe [ 52 ], Artemisia princeps [ 63 ], and Typha angustifolia [ 64 ] were utilized. In addition to these, several biomolecules, such as biopolymers [ 65 ], starch [ 66 ], fibrinolytic enzyme [ 39 ], and amino acids [ 67 ] were used. The biological synthesis of nanoparticles depends on three factors, including (a) the solvent; (b) the reducing agent; and (c) the non-toxic material. The major advantage of biological methods is the availability of amino acids, proteins, or secondary metabolites present in the synthesis process, the elimination of the extra step required for the prevention of particle aggregation, and the use of biological molecules for the synthesis of AgNPs is eco-friendly and pollution-free. Biological methods seem to provide controlled particle size and shape, which is an important factor for various biomedical applications [ 68 ]. Using bacterial protein or plant extracts as reducing agents, we can control the shape, size, and monodispersity of the nanoparticles [ 9 ]. The other advantages of biological methods are the availability of a vast array of biological resources, a decreased time requirement, high density, stability, and the ready solubility of prepared nanoparticles in water [ 69 ].

The biological activity of AgNPs depends on the morphology and structure of AgNPs, controlled by size and shape of the particles [ 70 , 71 ]. As far as size and shape are concerned, smaller size and truncated-triangular nanoparticles seem to be more effective and have superior properties. Although many studies successfully synthesized AgNPs with different shape and size ranges, they still have certain limitations. To achieve control over morphology and structure, an excess of strong reducing agent such as sodium borohydride (NaBH 4 ) was used for the synthesis of monodisperse and uniform-sized silver colloids [ 72 ]. Compared to chemical methods, biological methods allow for more ease in the control of shape, size, and distribution of the produced nanoparticles by optimization of the synthesis methods, including the amount of precursors, temperature, pH, and the amount of reducing and stabilizing factors [ 9 , 73 ].

3. Characterization

The physicochemical properties of nanoparticles are important for their behavior, bio-distribution, safety, and efficacy. Therefore, characterization of AgNPs is important in order to evaluate the functional aspects of the synthesized particles. Characterization is performed using a variety of analytical techniques, including UV-vis spectroscopy, X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). Several qualified books and reviews have presented the principles and usage of various kinds of analytical techniques for the characterization of AgNPs; however, the basics of the important techniques used for the characterization of AgNPs are detailed below for ease of understanding. For example, characterization of AgNPs using various analytical techniques prepared from culture supernatant of Bacillus species was given in Figure 1 .

Characterization of silver nanoparticles (AgNPs) prepared from Bacillus species using various analytical techniques. ( A ) Characterization of AgNPs by X-diffraction spectra of AgNPs; ( B ) Fourier transform infrared spectra of AgNPs; ( C ) Measurement of size distribution of AgNPs by dynamic light scattering; ( D ) Scanning electron microscopy images of AgNPs; ( E ). Transmission electron microscopy images of AgNPs.

3.1. UV-Visible Spectroscopy

UV-vis spectroscopy is a very useful and reliable technique for the primary characterization of synthesized nanoparticles which is also used to monitor the synthesis and stability of AgNPs [ 74 ]. AgNPs have unique optical properties which make them strongly interact with specific wavelengths of light [ 75 ]. In addition, UV-vis spectroscopy is fast, easy, simple, sensitive, selective for different types of NPs, needs only a short period time for measurement, and finally a calibration is not required for particle characterization of colloidal suspensions [ 76 , 77 , 78 ]. In AgNPs, the conduction band and valence band lie very close to each other in which electrons move freely. These free electrons give rise to a surface plasmon resonance (SPR) absorption band, occurring due to the collective oscillation of electrons of silver nano particles in resonance with the light wave [ 79 , 80 , 81 , 82 , 83 , 84 ]. The absorption of AgNPs depends on the particle size, dielectric medium, and chemical surroundings [ 81 , 82 , 83 , 84 , 85 ]. Observation of this peak—assigned to a surface plasmon—is well documented for various metal nanoparticles with sizes ranging from 2 to 100 nm [ 74 , 86 , 87 ]. The stability of AgNPs prepared from biological methods was observed for more than 12 months, and an SPR peak at the same wavelength using UV-vis spectroscopy was observed.

3.2. X-ray Diffraction (XRD)

X-ray diffraction (XRD) is a popular analytical technique which has been used for the analysis of both molecular and crystal structures [ 79 , 88 ], qualitative identification of various compounds [ 89 ], quantitative resolution of chemical species [ 90 ], measuring the degree of crystallinity [ 91 ], isomorphous substitutions [ 92 ], particle sizes [ 93 ], etc. When X-ray light reflects on any crystal, it leads to the formation of many diffraction patterns, and the patterns reflect the physico-chemical characteristics of the crystal structures. In a powder specimen, diffracted beams typically come from the sample and reflect its structural physico-chemical features. Thus, XRD can analyze the structural features of a wide range of materials, such as inorganic catalysts, superconductors, biomolecules, glasses, polymers, and so on [ 94 ]. Analysis of these materials largely depends on the formation of diffraction patterns. Each material has a unique diffraction beam which can define and identify it by comparing the diffracted beams with the reference database in the Joint Committee on Powder Diffraction Standards (JCPDS) library. The diffracted patterns also explain whether the sample materials are pure or contain impurities. Therefore, XRD has long been used to define and identify both bulk and nanomaterials, forensic specimens, industrial, and geochemical sample materials [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ].

XRD is a primary technique for the identification of the crystalline nature at the atomic scale [ 10 , 14 , 88 , 105 ]. X-ray powder diffraction is a nondestructive technique with great potential for the characterization of both organic and inorganic crystalline materials [ 106 ]. This method has been used to measure phase identification, conduct quantitative analysis, and to determine structure imperfections in samples from various disciplines, such as geological, polymer, environmental, pharmaceutical, and forensic sciences. Recently, the applications have extended to the characterization of various nano-materials and their properties [ 106 ]. The working principle of X-ray diffraction is Bragg’s law [ 88 , 105 ]. Typically, XRD is based on the wide-angle elastic scattering of X-rays [ 10 , 14 , 88 , 107 , 108 , 109 ]. Although XRD has several merits, it has limited disadvantages, including difficulty in growing the crystals and the ability to get results pertaining only to single conformation/binding state [ 14 , 108 , 110 ]. Another drawback of XRD is the low intensity of diffracted X-rays compared to electron diffractions [ 110 , 111 ].

3.3. Dynamic Light Scattering

Physicochemical characterization of prepared nanomaterials is an important factor for the analysis of biological activities using radiation scattering techniques [ 10 , 14 , 112 ]. DLS can probe the size distribution of small particles a scale ranging from submicron down to one nanometer in solution or suspension [ 10 , 14 , 113 ]. Dynamic light scattering is a method that depends on the interaction of light with particles. This method can be used for the measurement of narrow particle size distributions, especially in the range of 2–500 nm [ 78 ]. Among the techniques for the characterization of nanoparticles, the most commonly used is DLS [ 114 , 115 , 116 ]. DLS measures the light scattered from a laser that passes through a colloid, and mostly relies on Rayleigh scattering from the suspended nanoparticles [ 117 ]. Next, the modulation of the scattered light intensity as a function of time is analyzed, and the hydrodynamic size of particles can be determined [ 118 , 119 , 120 ]. To evaluate the toxic potential of any nanomaterial, its characterization in solution is essential [ 11 ]. Therefore; DLS is mainly used to determine particle size and size distributions in aqueous or physiological solutions [ 12 ]. The size obtained from DLS is usually larger than TEM, which may be due to the influence of Brownian motion. DLS is a nondestructive method used to obtain the average diameter of nanoparticles dispersed in liquids. It has the special advantage of probing a large quantity of particles simultaneously; however, it has a number of sample-specific limitations [ 101 , 121 ].

3.4. Fourier Transform Infrared (FTIR) Spectroscopy

FTIR is able to provide accuracy, reproducibility, and also a favorable signal-to-noise ratio. By using FTIR spectroscopy, it becomes possible to detect small absorbance changes on the order of 10 −3 , which helps to perform difference spectroscopy, where one could distinguish the small absorption bands of functionally active residues from the large background absorption of the entire protein [ 122 , 123 , 124 , 125 , 126 , 127 , 128 ]. FTIR spectroscopy is frequently used to find out whether biomolecules are involved in the synthesis of nanoparticles, which is more pronounced in academic and industrial research [ 10 , 68 , 129 , 130 ]. Furthermore, FTIR has also been extended to the study of nano-scaled materials, such as confirmation of functional molecules covalently grafted onto silver, carbon nanotubes, graphene and gold nanoparticles, or interactions occurring between enzyme and substrate during the catalytic process [ 68 , 131 , 132 ]. Furthermore, it is a non-invasive technique. Finally, the advantages of FTIR spectrometers over dispersive ones are rapid data collection, strong signal, large signal-to-noise ratio, and less sample heat-up [ 133 ]. Recently, further advancement has been made in an FTIR method called attenuated total reflection (ATR)-FTIR spectroscopy [ 134 , 135 , 136 ]. Using ATR-FTIR, we can determine the chemical properties on the polymer surface, and sample preparation is easy compared to conventional FTIR [ 10 , 137 , 138 , 139 , 140 , 141 ]. Therefore, FTIR is a suitable, valuable, non-invasive, cost effective, and simple technique to identify the role of biological molecules in the reduction of silver nitrate to silver.

3.5. X-ray Photoelectron Spectroscopy (XPS)

XPS is a quantitative spectroscopic surface chemical analysis technique used to estimate empirical formulae [ 109 , 140 , 141 , 142 ]. XPS is also known as electron spectroscopy for chemical analysis (ESCA), [ 141 ]. XPS plays a unique role in giving access to qualitative, quantitative/semi-quantitative, and speciation information concerning the sensor surface [ 143 ]. XPS is performed under high vacuum conditions. X-ray irradiation of the nanomaterial leads to the emission of electrons, and the measurement of the kinetic energy and the number of electrons escaping from the surface of the nanomaterials gives XPS spectra [ 109 , 140 , 141 , 142 ]. The binding energy can be calculated from kinetic energy. Specific groups of starburst macromolecules such as P=S, aromatic rings, C–O, and C=O can be identified and characterized by XPS [ 144 ].

3.6. Scanning Electron Microscopy

Recently, the field of nanoscience and nanotechnology has provided a driving force in the development of various high-resolution microscopy techniques in order to learn more about nanomaterials using a beam of highly energetic electrons to probe objects on a very fine scale [ 145 , 146 , 147 ]. Among various electron microscopy techniques, SEM is a surface imaging method, fully capable of resolving different particle sizes, size distributions, nanomaterial shapes, and the surface morphology of the synthesized particles at the micro and nanoscales [ 10 , 117 , 137 , 148 , 149 ]. Using SEM, we can probe the morphology of particles and derive a histogram from the images by either by measuring and counting the particles manually, or by using specific software [ 117 ]. The combination of SEM with energy-dispersive X-ray spectroscopy (EDX) can be used to examine silver powder morphology and also conduct chemical composition analysis. The limitation of SEM is that it is not able to resolve the internal structure, but it can provide valuable information regarding the purity and the degree of particle aggregation. The modern high-resolution SEM is able to identify the morphology of nanoparticles below the level of 10 nm.

3.7. Transmission Electron Microscopy

TEM is a valuable, frequently used, and important technique for the characterization of nanomaterials, used to obtain quantitative measures of particle and/or grain size, size distribution, and morphology [ 10 , 109 , 150 ]. The magnification of TEM is mainly determined by the ratio of the distance between the objective lens and the specimen and the distance between objective lens and its image plane [ 150 ]. TEM has two advantages over SEM: it can provide better spatial resolution and the capability for additional analytical measurements [ 10 , 148 , 150 ]. The disadvantages include a required high vacuum, thin sample section [ 10 , 109 , 148 ], and the vital aspect of TEM is that sample preparation is time consuming. Therefore, sample preparation is extremely important in order to obtain the highest-quality images possible.

3.8. Atomic Force Microscopy

Generally, AFM is used to investigate the dispersion and aggregation of nanomaterials, in addition to their size, shape, sorption, and structure; three different scanning modes are available, including contact mode, non-contact mode, and intermittent sample contact mode [ 10 , 14 , 151 , 152 , 153 , 154 , 155 ]. AFM can also be used to characterize the interaction of nanomaterials with supported lipid bilayers in real time, which is not achievable with current electron microscopy (EM) techniques [ 113 ]. In addition, AFM does not require oxide-free, electrically conductive surfaces for measurement, does not cause appreciable damage to many types of native surfaces, and it can measure up to the sub-nanometer scale in aqueous fluids [ 156 , 157 ]. However, a major drawback is the overestimation of the lateral dimensions of the samples due to the size of the cantilever [ 158 , 159 ]. Therefore, we have to provide much attention to avoid erroneous measurements [ 160 ]. Furthermore, the choice of operating mode—no contact or contact—is a crucial factor in sample analysis [ 160 ].

3.9. Localized Surface Plasmon Resonance (LSPR)

LSPR is a coherent, collective spatial oscillation of the conduction electrons in a metallic nanoparticle, which can be directly excited by near-visible light. The localized surface plasmon resonance (LSPR) condition is defined by several factors, including the electronic properties of the nanoparticle, the size and shape of the particle, temperature, the dielectric environment, and so on. Small changes in the local dielectric environment cause the dysfunction of LSPR. The frequency of the LSPR spectral peak is very sensitive to the nanostructure environment through the local refractive index. Thereby, shifts of the LSPR frequency are widely used as a method for the detection of molecular interaction close to the surface of the nanoparticle [ 161 , 162 , 163 , 164 , 165 , 166 ]. In addition, the near-field enhancement has led to a very large variety of advances in many fundamental and applied areas of science, particularly for the determination of nanoparticle shapes, dimensions, and compositions. This spectroscopy method is being used to investigate fundamental properties and processes of nanoparticles in (bio)-molecular detection devices, or (bio)-imaging tools with improved single-molecule sensitivity. LSPR spectroscopy can provide thermodynamic and real-time kinetic data for binding processes. LSPR-based tools will be helpful to analyze faster and with higher sensitivity. The application of LSPR spectroscopy is mainly used for biological and chemical sensing by transducing changes in the local refractive index via a wavelength-shift measurement, due to its sensitivity, wavelength tunability, smaller sensing volumes, and lower instrumentation cost. Single-nanoparticle LSPR spectroscopy is an important tool for understanding the relationship between local structure and spectra. In addition, single nanoparticles can provide even higher refractive-index sensitivity than nanoparticle arrays.

4. Properties of AgNPs

Physical and chemical properties of AgNPs—including surface chemistry, size, size distribution, shape, particle morphology, particle composition, coating/capping, agglomeration, dissolution rate, particle reactivity in solution, efficiency of ion release, cell type, and finally type of reducing agents used for synthesis—are crucial factors for determination of cytotoxicity [ 15 , 50 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 ]. For example, using biological reducing agents such as culture supernatants of various Bacillus species, AgNPs can be synthesized in various shapes, such as spherical, rod, octagonal, hexagonal, triangle, flower-like, and so on ( Figure 2 ). Previous studies supported the assertion that smaller size particles could cause more toxicity than larger, because they have larger surface area [ 176 ]. Shape is equally important to the determination of toxicity [ 177 ]. For example, in the biomedical field, various types of nanostructures have been used, including nanocubes, nanoplates, nanorods, spherical nanoparticles, flower-like, and so on [ 175 , 178 ]. AgNP toxicity mainly depends on the availability of chemical and or biological coatings on the nanoparticle surface [ 179 ]. AgNP surface charges could determine the toxicity effect in cells. For instance, the positive surface charge of these NPs renders them more suitable, allowing them to stay for a long time in blood stream compared to negatively-charged NPs [ 180 ], which is a major route for the administration of anticancer agents [ 181 , 182 ].

Biological synthesis of various shapes of AgNPs using culture supernatant of various Bacillus species. ( A ) Spherical; ( B ) mixed populations (octagonal, rod, hexagonal, and icosahedral); ( C ) highly branched; ( D ) flower-like in shape.

5. Biological Applications of AgNPs

Due to their unique properties, AgNPs have been used extensively in house-hold utensils, the health care industry, and in food storage, environmental, and biomedical applications. Several reviews and book chapters have been dedicated in various areas of the application of AgNPs. Herein, we are interested in emphasizing the applications of AgNPs in various biological and biomedical applications, such as antibacterial, antifungal, antiviral, anti-inflammatory, anti-cancer, and anti-angiogenic. Herein, we specifically addressed previously-published seminal papers and end with recent updates. A schematic diagram representing various applications of AgNPs is provided in Figure 3 .

Various applications of AgNPs.

5.1. Antibacterial Activity of AgNPs

AgNPs seem to be alternative antibacterial agents to antibiotics and have the ability to overcome the bacterial resistance against antibiotics. Therefore, it is necessary to develop AgNPs as antibacterial agents. Among the several promising nanomaterials, AgNPs seem to be potential antibacterial agents due to their large surface-to-volume ratios and crystallographic surface structure. The seminal paper reported by Sondi and Salopek-Sondi [ 6 ] demonstrated the antimicrobial activity of AgNPs against Escherichia coli , in which E. coli cells treated with AgNPs showed the accumulation of AgNPs in the cell wall and the formation of “pits” in the bacterial cell walls, eventually leading to cell death. In the same E. coli strain, smaller particles with a larger surface-to-volume ratio showed a more efficient antibacterial activity than larger particles [ 183 ]. Furthermore, the antibacterial activity of AgNPs is not only size—but also shape-dependent [ 70 ]. AgNPs were synthesized by four different types of saccharides with an average size of 25 nm, showing high antimicrobial and bactericidal activity against Gram-positive and Gram-negative bacteria, including highly multi-resistant strains such as methicillin-resistant Staphylococcus aureus . As mentioned previously, not only the size is important for determining the efficiency, but also shape, because AgNPs undergo a shape-dependent interaction with the Gram-negative organism E. coli [ 71 ]. Furthermore, a detailed study was carried out to investigate the efficiency of the antimicrobial effects of AgNPs against yeast, E. coli , and Staphylococcus aureus . The results suggest that at low concentrations of AgNPs, the complete inhibition of growth was observed in yeast and E. coli , whereas a mild effect was observed in S. aureus [ 184 ]. Biologically synthesized AgNPs from the culture supernatants of Klebsiella pneumoniae were evaluated; the efficiencies of various antibiotics, such as penicillin G, amoxicillin, erythromycin, clindamycin, and vancomycin against Staphylococcus aureus and E. coli were increased in the presence of Ag-NPs [ 185 ]. When compared to AgNPs, hydrogel–silver nanocomposites showed excellent antibacterial activity against E. coli . One-pot synthesis of chitosan–Ag–nanoparticle composite was found to have higher antimicrobial activity than its components at their respective concentrations, because one-pot synthesis favors the formation of small AgNPs attached to the polymer, which can be dispersed in media of pH ≤ 6.3 [ 186 ]. Biologically produced AgNPs using culture supernatants of Staphylococcus aureus showed significant antimicrobial activity against methicillin-resistant S. aureus , followed by methicillin-resistant Staphylococcus epidermidis and Streptococcus pyogenes , whereas only moderate antimicrobial activity was observed against Salmonella typhi and Klebsiella pneumoniae [ 187 ]. The mechanisms of AgNP-induced cell death was observed in E. coli through the leakage of reducing sugars and proteins. Furthermore, AgNPs are able to destroy the permeability of the bacterial membranes via the generation of many pits and gaps, indicating that AgNPs could damage the structure of the bacterial cell membrane [ 2 ]. Silver nanocrystalline chlorhexidine (AgCHX) complex showed strong antibacterial activity against the tested Gram-positive/negative and methicillin-resistant Staphylococcus aureus (MRSA) strains. Interestingly, the minimal inhibitory concentrations (MICs) of nanocrystalline Ag(III)CHX were much lower than those of the ligand (CHX), AgNO 3 , and the gold standard, silver sulfadiazine [ 188 ].

Biofilms are not only leads to antimicrobial resistance, but are involved in the development of ocular-related infectious diseases, such as microbial keratitis [ 189 ]. Kalishwaralal and co-workers demonstrated the potential anti-biofilm activity against Pseudomonas aeruginosa and Staphylococcus epidermidis . Similarly, guava leaf extract reduced AgNPs (Gr-Ag-NPs) showed significant antibacterial activity and stability against E. coli compared to chemically synthesized AgNPs; the reason for this higher activity could be the adsorption of biomolecules on the surface of the Gr-Ag-NPs [ 190 ]. AgNPs synthesized by Cryphonectria sp. showed antibacterial activity against various human pathogenic bacteria, including S. aureus , E. coli , Salmonella typhi , and Candida albicans . Interestingly, these particular AgNPs exhibited higher antibacterial activity against both S. aureus and E. coli than against S. typhi and C. albicans . Figure 4 shows the effectiveness of dose-dependent antibacterial activity of biologically synthesized AgNPs in E. coli.

Dose-dependent antibacterial activity of biologically synthesized AgNPs in E. coli. CON: control.

Besinis et al. [ 191 ] compared the toxic efficiency of different nanomaterials, such as AgNPs, silver, and titanium dioxide against routine disinfectant chlorhexidine in Streptococcus mutans . Among various nanomaterials, AgNPs had the strongest antibacterial activity of the NPs tested. Agnihotri et al. [ 192 ] demonstrated that the mechanisms of AgNPs on bactericidal action using AgNPs immobilized on an amine-functionalized silica surface. They found that contact killing is the predominant bactericidal mechanism, and surface-immobilized nanoparticles show greater efficacy than colloidal AgNPs, as well as a higher concentration of silver ions in solution. The nanocomposite containing silver/polyrhodanine nanocomposite-decorated silica nanoparticles shows potential and enhanced antibacterial activity against E. coli and S. aureus , which is due to the particular combination of AgNPs and the polyrhodanine [ 155 ]. Interestingly, Khurana et al. [ 193 ] investigated the antimicrobial properties of silver based on its physical and surface properties against S. aureus , B. megaterium , P. vulgaris , and S. sonnei . The enhancement of antibacterial action was observed with particles having a hydrodynamic size of 59 nm compared to 83 nm. Gurunathan et al. [ 68 ] reported that the antibacterial and anti-biofilm activity of antibiotics, AgNPs, or combinations of AgNPs against important pathogenic bacteria Pseudomonas aeruginosa , Shigella flexneri , Staphylococcus aureus , and Streptococcus pneumoniae . The results suggest that, the combination of both antibiotics and AgNPs showed significant antimicrobial and anti-biofilm effects at the lowest concentration of antibiotics and AgNPs compared to AgNPs or antibiotics alone. Nanocomposite spheres composed of AgNPs decorated on the polymer colloids exhibited excellent antibacterial activity [ 194 ]. Recently, nanocomposites containing graphene and AgNPs showed much interest in antibacterial activity. Graphene oxide (GO)-Ag nanocomposite showed enhanced antibacterial activity against E. coli and S. aureus using the conventional plate count method and disk diffusion method [ 195 ]. The GO-Ag nanocomposite exhibited an excellent antibacterial activity against methicillin-resistant S. aureus , Acinetobacter baumannii , Enterococcus faecalis , and Escherichia coli . In addition, GO-Ag nanocomposite is a promising antibacterial agent against common nosocomial bacteria, particularly antibiotic-resistant MRSA [ 196 ]. AgNPs derived from fungal extracts as reducing agents (F-AgNPs) showed enhanced antibacterial activity both in Pseudomonas aeruginosa and Staphylococcus aureus when compared to AgNPs derived from the culture supernatant of bacteria (B-AgNPs) ( Figure 5 ). The minimum inhibitory concentration of F-AgNPs is lesser than B-AgNPs. Nano-silver interacts with peptides and bacteria and serves as nanomedicine in various bacteria, fungi, and virus-mediated diseases [ 197 ].

Differential antibacterial activity of AgNPs synthesized with Calocybe indica extracts (F-AgNPs) and the culture supernatant of Bacillus tequilensis (B-AgNPs) as reducing agents.

5.2. Antifungal Activity of AgNPs

Fungal infections are more frequent in patients who are immunosuppressed, and overcoming fungi-mediated diseases is a tedious process, because currently there is a limited number of available antifungal drugs [ 198 ]. Therefore, there is an inevitable and urgent need to develop antifungal agents, which should be biocompatible, non-toxic, and environmentally friendly. At this juncture, AgNPs play an important role as anti-fungal agents against various diseases caused by fungi. Nano-Ag showed potent anti-fungal activity against clinical isolates and ATCC strains of Trichophyton mentagrophytes and Candida species with concentrations of 1–7 μg/mL. Esteban-Tejeda et al. [ 199 ] developed an inert matrix containing AgNPs with an average size of 20 nm into a soda-lime glass which shows enhanced biocidal activity. Monodisperse Nano-Ag sepiolite fibers showed significant antifungal activity against Issatchenkia orientalis . AgNPs exhibited good antifungal activity against Aspergillus niger and a MIC of 25 μg/mL against Candida albicans [ 200 ]. Biologically-synthesized AgNPs showed enhanced antifungal activity with fluconazole against Phoma glomerata , Phoma herbarum , Fusarium semitectum , Trichoderma sp., and Candida albicans [ 201 ]. AgNPs stabilized by sodium dodecyl sulfate showed enhanced antifungal activity against Candida albicans compared to conventional antifungal agents [ 20 ]. The size-dependent antifungal activities of different AgNPs were performed against mature Candida albicans and Candida glabrata biofilms. Biologically synthesized AgNPs exhibited antifungal activity against several phytopathogenic fungi, including Alternaria alternata , Sclerotinia sclerotiorum , Macrophomina phaseolina , Rhizoctonia solani , Botrytis cinerea , and Curvularia lunata at the concentration of 15 mg [ 202 , 203 ]. Similarly, The AgNPs synthesized by Bacillus species exhibited strong antifungal activity against the plant pathogenic fungus Fusarium oxysporum at the concentration of 8 μg/mL [ 204 ]. Carbon nanoscrolls (CNSs) composed of graphene oxides and AgNPs exhibited enhanced and prolonged antifungal activity against Candida albicans and Candida tropical compared to GO–AgNP nanocomposites containing graphene oxide and AgNPs [ 205 ]. The antifungal efficacy of AgNPs was evaluated in combination with nystatin (NYT) or chlorhexidine (CHX) against Candida albicans and Candida glabrata biofilms. The results from this investigation suggest that AgNPs combined with either nystatin (NYT) or chlorhexidine digluconate (CHG) showed better synergistic anti-biofilm activity; however, this activity depends on the species and drug concentrations [ 206 ].

The biologically synthesized AgNPs exhibited strong antifungal activity against Bipolaris sorokiniana by the inhibition of conidial germination [ 207 ]. Interestingly, AgNPs not only inhibit human and plant pathogenic fungi, but also indoor fungal species such as Penicillium brevicompactum , Aspergillus fumigatus , Cladosporium cladosporoides , Chaetomium globosum , Stachybotrys chartarum , and Mortierella alpine cultured on agar media [ 208 ].

5.3. Antiviral Activity of AgNPs

Viral mediated diseases are common and becoming more prominent in the world; therefore, developing anti-viral agents is essential. The mechanisms of the antiviral activity of AgNPs are an important aspect in antiviral therapy. AgNPs have unique interactions with bacteria and viruses based on certain size ranges and shapes [ 70 , 209 , 210 ]. The antiviral activity nano-Ag incorporated into polysulfone ultrafiltration membranes (nAg-PSf) was evaluated against MS2 bacteriophage, which shows that significant antiviral activity was a result of increased membrane hydrophilicity [ 21 ]. Lara et al. [ 211 ] showed the first mechanistic study demonstrating anti-HIV activity at an early stage of viral replication. Poly vinyl pyrrolidone (PVP)-coated AgNPs prevented the transmission of cell-associated HIV-1 and cell-free HIV-1 isolates [ 211 ]. AgNPs have demonstrated efficient inhibitory activities against human immunodeficiency virus (HIV) and hepatitis B virus (HBV) [ 212 ]. A study was attempted to investigate the antiviral action of the AgNPs; the data showed that both macrophage (M)-tropic and T-lymphocyte (T)-tropic strains of HIV-1 were highly sensitive to the AgNP-coated polyurethane condom (PUC) [ 213 ]. Although several studies have shown that AgNPs could inhibit the viability of viruses, the exact mechanism of antiviral activity is still obscure. However, the studies from Trefry and Wooley found that AgNPs caused a four- to five-log reduction in viral titer at concentrations that were not toxic to cells [ 214 ]. Interestingly, in the presence of AgNPs, virus was capable of adsorbing to cells, and this viral entry is responsible for the antiviral effects of AgNPs. Hemagglutination assay indicated that AgNPs could significantly inhibit the growth of the influenza virus in Madin-Darby canine kidney cells. The study from intranasal AgNP administration in mice significantly enhanced survival, lower lung viral titer levels, minor pathologic lesions in lung tissue, and remarkable survival advantage after infection with the H3N2 influenza virus, suggesting that AgNPs had a significant role in mice survival [ 215 ]. Biologically-synthesized AgNPs inhibited the viability in herpes simplex virus (HSV) types 1 and 2 and human parainfluenza virus type 3, based on size and zeta potential of AgNPs [ 216 ]. The treatment of Vero cells with non-cytotoxic concentrations of AgNPs significantly inhibited the replication of Peste des petits ruminants virus (PPRV). The mechanisms of viral replication are due to the interaction of AgNPs with the virion surface and the virion core [ 217 ]. Tannic acid mediated the synthesis of various sizes of AgNPs capable of reducing HSV-2 infectivity both in vitro and in vivo through direct interaction, blocked virus attachment, penetration, and further spread [ 218 ]. The antiviral property of Ag + alone and a combination of 50 ppb Ag + and 20 ppm CO 3 2− (carbonate ions) was performed on bacteriophage MS2 phage. The results from this study showed that 50 ppb Ag + alone was unable to affect the phage, and the combination of 50 ppb Ag + and 20 ppm CO 3 was found to have an effective antiviral property within a contact time of 15 min [ 219 ]. Treatment with AgNPs for 24 h in Bean Yellow Mosaic Virus (BYMV) decreased virus concentration, percentage of infection, and disease severity [ 220 ].

5.4. Anti-Inflammatory Activity of AgNPs

Inflammation is an early immunological response against foreign particles by tissue, which is supported by the enhanced production of pro-inflammatory cytokines, the activation of the immune system, and the release of prostaglandins and chemotactic substances such as complement factors, interleukin-1 (IL-1), TNF-α, and TGF-β [ 221 , 222 , 223 , 224 ]. In order to overcome inflammatory action, we need to find effective anti-inflammatory agents. Among several anti-inflammatory agents, AgNPs have recently played an important role in anti-inflammatory field. AgNPs have been known to be antimicrobial, but the anti-inflammatory responses of AgNPs are still limited. Bhol and Schechter [ 225 ] reported the anti-inflammatory activity in rat. Rats treated intra-colonically with 4 mg/kg or orally with 40 mg/kg of nanocrystalline silver (NPI 32101) showed significantly reduced colonic inflammation. Mice treated with AgNPs showed rapid healing and improved cosmetic appearance, occurring in a dose-dependent manner. Furthermore, AgNPs showed significant antimicrobial properties, reduction in wound inflammation, and modulation of fibrogenic cytokines [ 226 ]. Continuing the previous study, Wong et al. [ 222 ] investigated to gain further evidence for the anti-inflammatory properties of AgNPs, in which they used both in vivo and in vitro models and found that AgNPs are able to down-regulate the quantities of inflammatory markers, suggesting that AgNPs could suppress inflammatory events in the early phases of wound healing [ 222 ]. A porcine contact dermatitis model showed that treatment with nanosilver significantly increases apoptosis in the inflammatory cells and decreased the levels of pro-inflammatory cytokines [ 227 ]. Biologically-synthesized AgNPs can inhibit the production of cytokines induced by UV-B irradiation in HaCaT cells, and also reduces the edema and cytokine levels in the paw tissues [ 228 ].

5.5. Anti-Angiogenic Activity of AgNPs

Pathological angiogenesis is a symbol of cancer and various ischemic and inflammatory diseases [ 229 ]. There are several research groups interested in discovering novel pro- and anti-angiogenic molecules to overcome angiogenic-related diseases. Although there are several synthetic molecules having anti-angiogenic properties, the discovery of a series of natural pro- and anti-angiogenic factors suggests that this may provide a more physiological approach to treat both classes of angiogenesis-dependent diseases in the near future [ 230 ]. Recently, several studies provided supporting evidence using both in vitro and in vivo models showing that AgNPs have both anti-angiogenic and anti-cancer properties. Herein, we wish to summarize the important contribution in cancer and other angiogenic related diseases.

Kalishwaralal et al. [ 231 ] demonstrated the anti-angiogenic property of biologically synthesized AgNPs using bovine retinal endothelial cells (BRECs) as a model system, in which they found the inhibition of proliferation and migration in BRECs after 24 h of treatment with AgNPs at 500 nM concentration. The mechanisms of inhibition of vascular endothelial growth factor (VEGF) induced angiogenic process by the activation of caspase-3 and DNA fragmentation, and AgNPs inhibited the VEGF-induced PI3K/Akt pathway in BRECs [ 232 ]. Followed by this study, Gurunathan et al. [ 23 ] provided evidence for the anti-angiogenic property of AgNPs by using pigment epithelium derived factor (PEDF) as a bench mark, which is known as a potent anti-angiogenic agent. Using BRECs as an in vitro model system, they found that AgNPs inhibited VEGF-induced angiogenic assays. Furthermore, they demonstrated that AgNPs could block the formation of new blood microvessels by the inactivation of PI3K/Akt. The same group also demonstrated the anticancer property of AgNPs using various cytotoxicity assays in Dalton’s lymphoma ascites (DLA) cells, and a tumor mouse model showed significantly increased survival time in the presence of AgNPs [ 24 ]. AgNPs reduced with diaminopyridinyl (DAP)-derivatized heparin (HP) polysaccharides (DAPHP) inhibited basic fibroblast growth factor (FGF-2)-induced angiogenesis compared to glucose conjugation [ 232 ]. Kim et al. [ 233 ] developed an anti-angiogenic Flt1 peptide conjugated to tetra- N -butyl ammonium modified hyaluronate (HA-TBA), and it was used to encapsulate genistein. Using human umbilical vein endothelial cells (HUVECs) as in vitro model system, they found that genistein/Flt1 peptide–HA micelle inhibited the proliferation of HUVECs, and the same reagents could drastically reduce corneal neovascularization in silver nitrate-cauterized corneas of Sprague Dawley (SD) rats. Ag 2 S quantum dots (QDs) used as nanoprobes to monitor lymphatic drainage and vascular networks. Ag 2 S-based nanoprobes showed long circulation time and high stability. In addition, they were able to track angiogenesis mediated by a tiny tumor (2–3 mm in diameter) in vivo [ 5 ]. Recently, Achillea biebersteinii flowers extract-mediated synthesis of AgNPs containing a concentration of 200 μg/mL showed a 50% reduction in newly-formed vessels [ 234 ]. Figure 6 shows the inhibitory effect of AgNPs on VEGF induced angiogenic activity in bovine retinal endothelial cells (BRECs) and human breast cancer cells MDA-MB 231.

Effect of AgNPs on vascular endothelial growth factor (VEGF)-induced proliferation of ( A ) bovine retinal endothelial cells (BRECs); and ( B ) human breast cancer cells MDA-MB 231. Cells were treated with VEGF with or without AgNPs for 24 h. Cell proliferation was determined by trypan blue exclusion assay.

5.6. Anticancer Activity of AgNPs

In our lifetime, 1 in 3 people has the possibility to develop cancer [ 235 ]. Although many chemotherapeutic agents are currently being used on different types of cancers, the side effects are enormous, and particularly, administrations of chemotherapeutic agents by intravenous infusion are a tedious process [ 235 ]. Therefore, it is indispensable to develop technologies to avoid systemic side effects. At this juncture, many researchers are interested in developing nanomaterials as an alternative tool to create formulations that can target tumor cells specifically. Several research laboratories have used various cell lines to address the possibility of finding a new molecule to battle cancer. Here we summarized the work from various laboratories reporting anticancer activity using both in vitro and in vivo model systems. Gopinath et al. [ 236 ] investigated the molecular mechanism of AgNPs and found that programmed cell death was concentration-dependent under conditions. Further, they observed a synergistic effect on apoptosis using uracil phosphoribosyltransferase (UPRT)-expressing cells and non-UPRT-expressing cells in the presence of fluorouracil (5-FU). In these experimental conditions, they observed that AgNPs not only induce apoptosis but also sensitize cancer cells. The anticancer property of starch-coated AgNPs was studied in normal human lung fibroblast cells (IMR-90) and human glioblastoma cells (U251). AgNPs induced alterations in cell morphology, decreased cell viability and metabolic activity, and increased oxidative stress leading to mitochondrial damage and increased production of reactive oxygen species (ROS), ending with DNA damage. Among these two cell types, U251 cells showed more sensitivity than IMR-90 [ 237 ]. The same group also demonstrated that the cellular uptake of AgNPs occurred mainly through endocytosis. AgNP-treated cells exhibited various abnormalities, including upregulation of metallothionein, downregulation of major actin binding protein, filamin, and mitotic arrest [ 237 ]. The morphology analysis of cancer cells suggests that biologically synthesized AgNPs could induce cell death very significantly. Jun et al. [ 238 ] elegantly prepared multifunctional silver-embedded magnetic nanoparticles, in which the first type consist of silver-embedded magnetic NPs with a magnetic core of average size 18 nm and another type consist of a thick silica shell with silver having an average size of 16 nm; the resulting silica-encapsulated magnetic NPs (M-SERS dots) produce strong surface-enhanced Raman scattering (SERS) signals and have magnetic properties, and these two significant properties were used for targeting breast-cancer cells (SKBR3) and floating leukemia cells (SP2/O).

The antineoplastic activities of protein-conjugated silver sulfide nano-crystals are size dependent in human hepatocellular carcinoma Bel-7402 and C6 glioma cells [ 239 ]. Instead of giving direct treatment of AgNPs into the cells, some researchers developed chitosan as a carrier molecule for the delivery of silver to the cancer cells. For example, Sanpui et al. [ 240 ] demonstrated that chitosan-based nanocarrier (NC) delivery of AgNPs induces apoptosis at very low concentrations. They then examined cytotoxic efficiency using a battery of biochemical assays. They found an increased level of intracellular ROSin HT 29 cells. Lower concentrations of nanocarrier with AgNPs showed better inhibitory results than AgNPs alone. Boca et al. [ 241 ] reported that chitosan-coated silver nanotriangles (Chit-AgNTs) show an increased cell mortality rate. In addition, human embryonic cells (HEK) were able to take up Chit-AgNTs efficiently, and the cytotoxic effect of various sizes of AgNPs was significant in acute myeloid leukemia (AML) cells [ 242 ]. Recently, the anticancer property of bacterial (B-AgNPs) and fungal extract-produced AgNPs (F-AgNPs) was demonstrated in human breast cancer MDA-MB-231 cells. Both biologically produced AgNPs exhibited significant cytotoxicity [ 62 , 243 ]. Among these two AgNPs, fungal extract-derived AgNPs had a stronger effect than B-AgNPs, which is due to the type of reducing agents used for the synthesis of AgNPs. Similarly, AgNPs derived from Escherichia fergusoni showed dose-dependent cytotoxicity against MCF-7 cells [ 62 ]. Plant extract-mediated synthesis of AgNPs showed more pronounced toxic effect in human lung carcinoma cells (A549) than non-cancer cells like human lung cells, indicating that AgNPs could target cell-specific toxicity, which could be the lower level of pH in the cancer cells [ 63 ]. Targeted delivery is an essential process for the treatment of cancer. To address this issue, Locatelli et al. [ 244 ] developed multifunctional nanocomposites containing polymeric nanoparticles (PNPs) containing alisertib (Ali) and AgNPs. PNPs conjugated with a chlorotoxin (Ali@PNPs–Cltx) showed a nonlinear dose–effect relationship, whereas the toxicity of Ag/Ali@PNPs–Cltx remained stable. Biologically synthesized AgNPs showed significant toxicity in MCF7 and T47D cancer cells by higher endocytic activity than MCF10-A normal breast cell line [ 245 ]. Banti and Hadjikakou explained the detailed account of anti-proliferative and anti-tumor activity of silver(I) compounds [ 246 ]. Biologically synthesized AgNPs capable of altering cell morphology of cancer cells ( Figure 7 ), which is an early indicator for apoptosis. Apoptosis can be determined by structural alterations in cells by transmitted light microscopy.

Anticancer activity of biologically synthesized AgNPs using Bacillus species in human ovarian cancer and human breast cancer cells.

5.7. Diagnostic, Biosensor, and Gene Therapy Applications of AgNPs

The advancement in medical technologies is increasing. There is much interest in using nanoparticles to improve or replace today’s therapies. Nanoparticles have advantages over today’s therapies, because they can be engineered to have certain properties or to behave in a certain way. Recent developments in nanotechnology are the use of nanoparticles in the development of new and effective medical diagnostics and treatments. The ability of AgNPs in cellular imaging in vivo could be very useful for studying inflammation, tumors, immune response, and the effects of stem cell therapy, in which contrast agents were conjugated or encapsulated to nanoparticles through surface modification and bioconjugation of the nanoparticles. Silver plays an important role in imaging systems due its stronger and sharper plasmon resonance. AgNPs, due to their smaller size, are mainly used in diagnostics, therapy, as well as combined therapy and diagnostic approaches by increasing the acoustic reflectivity, ultimately leading to an increase in brightness and the creation of a clearer image [ 247 , 248 ]. Nanosilver has been intensively used in several applications, including diagnosis and treatment of cancer and as drug carriers [ 249 , 250 , 251 ]. Nanosilver was used in combination with vanadium oxide in battery cell components to improve the battery performance in next-generation active implantable medical devices [ 250 ]. Recently, silver has been used to develop silver-based biosensors for the clinical detection of serum p53 in head and neck squamous cell carcinoma [ 252 ]. In addition, it has been explored for the location of cancer cells, and can absorb light and selectively destroy targeted cancer cells through photothermal therapy [ 253 ].

6. Mechanism of the Anti-Cancer Activity of AgNPs

The next interesting aspect of silver is to find out the mechanism of AgNP-induced apoptosis in cancer cells. In this context, AshaRani et al. [ 254 ] investigated the cellular and molecular mechanisms of nanoparticle-induced effects using normal human lung cells IMR-90 and human brain cancer cells U251. They found that AgNPs were capable of adsorbing cytosolic proteins on their surface that may influence the function of intracellular factors, and that they can regulate gene expression and pro-inflammatory cytokines. Foldbjerg et al. [ 255 ] addressed the interesting aspect of cellular transcriptome analysis upon exposure of human lung epithelial cell line A549 using microarray analysis. The results from this study exhibited that AgNPs could alter the regulation of more than 1000 genes. Among several genes, metallothionein, heat shock protein, and histone families were significant [ 255 ]. Recently, autophagy-induced cell death has been another identified mechanism for the anti-cancer activity of AgNPs. Autophagy induced by nanoparticles is a critical cellular degradation process, and elevated autophagy could promote cell death [ 256 ]. Our recent findings show that AgNPs are capable of inducing autophagy through the accumulation of autophagolysosmes in human ovarian cancer cells ( Figure 8 ). Therefore, autophagy can have a dual function; at lower levels, it can enhance the cell survival, and at elevated levels, it can cause cell death. Therefore, the use of autophagy inhibitors or autophagy protein-5 (ATG5)—small interfering RNAs (siRNA) enhanced AgNPs induced cell death in cancer cells.

Biologically synthesized AgNPs using Bacillus species induce accumulation of autophagolysosomes in human ovarian cancer cells.

The antitumor activity of AgNPs was significantly enhanced in B16 mouse melanoma cells by the inhibition of autophagy using wortmanin [ 256 ]. One of the most important mechanisms of the toxicity of AgNPs is that excessive levels of intracellular ion concentration increases the production of ROS, which is produced by cellular oxygen metabolism [ 15 , 68 ]. On other hand, uncontrolled ROS production can lead to serious cellular injuries [ 15 ], such as DNA damage and mitochondria-involved apoptotic cell death [ 1 , 257 , 258 , 259 ]. Recently, De Matteis et al. [ 260 ] proposed that endocytosed AgNPs are degraded in the lysosomes, and the release of Ag + ions in the cytosol induces cell damages. Hatipoglu et al. [ 261 ] revealed that the cytotoxicity and genotoxicity of AgNPs depends on reaction times for the preparation of AgNPs. The conclusion drawn from this study suggests that AgNP seeds were the major source of toxicity. Gurunathan et al. [ 1 ] reported that cytotoxicity of AgNPs in human breast cancer cells MDA-MB-231 via the activation of p53, p-Erk1/2, and caspase-3 signaling, and the downregulation of Bcl-2. Importantly, AgNP-mediated apoptosis was a p53-dependent pathway. On the other hand, Zuberek et al. [ 262 ] demonstrated that AgNPs not only induced oxidative stress, but also indicated the influence of energy supply from glucose availability in the media. They showed evidence by growing HepG2 cells in two different media with high (25 mM) or low (5.5 mM) glucose content in the presence of 20 nm AgNPs. In this assay, they observed that AgNPs induced the dose-dependent generation of H 2 O 2 . The study suggests that lower levels of glucose are responsible for defense mechanisms. All of these studies suggest that AgNPs can induce cell death through various processes, including ROS generation, enhanced leakage of lactate dehydrogenase, upregulation of apoptosis and autophagy genes, endoplasmic reticulum stress, mitochondrial dysfunction, activation of caspases, and DNA damage.

7. Therapeutic Approach for Cancer Treatment Using AgNPs

The application of AgNPs in cancer is divided into diagnostic and therapeutic purposes. Several laboratories have addressed the enhancement of the therapeutic usage of AgNPs as nanocarriers for targeted delivery, chemotherapeutic agents, and as enhancers for radiation and photodynamic therapy. Here we summarized the possible therapeutic approaches for cancer using AgNPs in cancer cell lines or animal models. For instance, Lim et al. [ 263 ] synthesized plasmonic magnetic nanoparticles to enhance MRI contrast consisting of multiple components of various nanoparticles in a single platform containing silver monolayer- gold-coated magnetic nanoparticles. These coated materials showed highly efficient killing of SKBr3 cells within 3 min of near-infrared laser at the relatively low exposure of 12.7 W/cm at 808 nm. To address the efficiency of photothermal therapy, Huang et al. [ 264 ] designed an aptamer-based nanostructure which combines the high absorption efficiency of Au–Ag nanorods showing excellent hyperthermia efficiency and selectivity. The combination of AgNPs with ligands strongly influences the toxicity and cellular uptake into the cells.

Recently, photo-based nanomedicine has gained much importance for cancer treatment among several approaches [ 265 ]. Khlebtsov et al. [ 266 ] developed multifunctional NPs which significantly induced cell death in HeLa cervical cancer cells. Wang et al. [ 267 ] developed folic acid (FA)-coated AgNPs with an average size of 23 ± 2 nm showing excellent receptor-mediated cellular uptake; with this compound (FA-AgNPs), they conjugated the chemotherapeutic drug doxorubicin (DOX) by electrostatic bonding. DOX was released efficiently, and cell death was observed after 8 h. They concluded that AgNPs can be used as nanocarriers for desired drugs for cancer treatment. To increase intracellular uptake and cytotoxicity in lymphoma cells, Fang et al. [ 268 ] designed self-assembled polymer–doxorubicin conjugates such as NP-Im/DOX, NP-Ag/DOX, and NP-Dm/DOX (Nanoparticles (NP), guanidinium group (Ag), an imidazole group (Im), and a tertiary amine group (Dm), doxorubicin (Dox)) using three different cationic side chains with an average of 80 nm for the efficient delivery of nanocarrier. Locatelli et al. [ 269 ] developed a nanocarrier by using a simple method, in which lipophilic AgNPs entrapped into PEG-based polymeric nanoparticles containing chlorotoxin. The interesting aspect using this nanocarrier showed enhanced cellular uptake and cytotoxic effect.

Recently, nanomaterials have been used for diagnosis, treatment, and prevention of cancer using photo-based therapeutic approaches [ 270 ]. The nanostructures are more capable of destroying the cancer cells than non-cancer cells at low irradiation power density [ 271 ]. In this context, Wu et al. [ 271 ] developed sensitive and specific detection aptamer-based Ag–Au shell–core nanostructure-photothermal therapy in which the nanostructures were able to target the cells with high affinity and specificity. The intra-tumoral administration of AgNPs in combination with a single dose of ionizing radiation enhanced therapeutic efficiency in C6 glioma-bearing rats [ 272 ]. Nanoparticles consisting of a silver nanoshell with a carbon core composite were significantly cytotoxic to cells in the presence of phototherapy and radiotherapy [ 273 ]. Combination of AgNPs–chitosan–para-aminothiophenol (pATP)–folic acid showed significant stability and targeted uptake in NIH:OVCAR-3 human ovarian cancer cell line. The efficient therapeutic approach was achieved by targeted cancer cell treatment with these composites [ 274 ]. Recently, Mukherjee et al. [ 275 ] used AgNPs as cancer theranostic agents; they prepared AgNPs from Olax scandens leaf extract and prepared AgNPs showing anticancer activity against various types of cancer cells, including A549, B16, and MCF7. Furthermore, they observed a bright red fluorescence signal from AgNPs, which can be exploited for localized drug delivery into the cancer cells. Considering the literature, AgNPs are not only used as drug delivery devices but they also serve as drugs; therefore, they are used for therapeutics [ 276 ]. AgNPs are well known antibacterial agents, and they also enhance the tumor-killing effects of anticancer drugs [ 276 ]. The combination of chemotherapeutic agents with nanoparticles is a developing effective approach for the eradication of cancer, in which they are using lower doses of drugs to reduce cytotoxic effects and increase the efficacy [ 277 ]. For example, the combination of Platinol (cisplatin) and Navelbine (vinorelbine) showed better efficiency in non-small cell lung cancer [ 278 ]. Combination of CPX-351 in a liposomal NP with cytarabine and daunorubicin showed better efficacy in the treatment of acute myeloid leukemia [ 279 ]. Similarly, the combination of salinomycin (Sal) with AgNPs derived from Typha angustifolia plant extracts showed a synergistic cytotoxic effect in human ovarian cancer cells ( Figure 9 ).

Morphological changes of the human ovarian cancer cell line A2780 after treatment with Salinimycin (Sal), AgNPs, and Sal plus AgNPs. A2780 cells were treated with Sal (3 μM), AgNPs (3μg/mL), and Sal plus AgNPs (3 μM plus 3 μg/mL) for 24 h, and the morphological changes of cells were observed under an inverted microscope (200×). The combination of Sal and AgNP induced significant morphological changes.

Altogether, published literatures suggest that the AgNPs is a suitable promising agent to inhibit the growth of cancer cells via various mechanistic approaches. The hypothetical mechanism is shown in Figure 10 .

The possible mechanisms of AgNP-induced cytotoxicity in cancer cell lines. Endoplasmic reticulum stress(ER), lactate dehydrogenase (LDH), reactive oxygen species (ROS).

8. Challenges for Cancer Therapy Using AgNPs

Nanomedicine is as one of the fast developing and promising strategies to combat cancer using metallic nanoparticles. Current treatment for cancer, such as chemo- and radiation therapy, has limitations due to unexpected drug-associated side effects, lack of specificity of low drug concentrations at the tumor target site, and the development of chemoresistance [ 280 , 281 ]. Nanoparticle-mediated therapy is the best, most suitable, and alternative therapeutic strategy in cancer therapy. Nanoparticles (NPs) have the ability to target through passive or active targeting of particular diseased cells or tumor tissues by the encapsulation of therapeutic agents with nanoparticles, and they have been used as drug delivery systems [ 282 ]. Although many nanoparticle-mediated strategies have been developed, heterogeneity of the tumor and its stroma is a significant challenge for nanotechnologists and clinicians to come up with specific formulations to precisely target specific cancer cells. To achieve higher specificity, reduction in toxicity, biocompatibility, safety, better efficacy, and to overcome the limitations of conventional chemotherapy, using new nanoparticles in single platform-based strategies is another challenge in cancer therapy. However, there is a need to address the challenges and limitations of using nanoparticles for cancer therapy; these include physiological barriers, limited carrying capacity, enhanced permeability and retention effect (EPR), variability of nanoparticles, and regulatory and manufacturing issues [ 282 ].

9. Conclusions and Future Perspectives

This review comprehensively addressed synthesis, characterization, and bio-applications of silver nanoparticles, with special emphasis on anticancer activity and its mechanisms and also therapeutic approaches for cancer using AgNPs. Recently, both academic and industrial research has explored the possibility of using AgNPs as a next-generation anticancer therapeutic agent, due to the conventional side effects of chemo- and radiation therapy. Although AgNPs play an important role in clinical research, several factors need to be considered, including the source of raw materials, the method of production, stability, bio-distribution, controlled release, accumulation, cell-specific targeting, and finally toxicological issues to human beings. The development of AgNPs as anti-angiogenic molecules is one of the most interesting approaches for cancer treatment and other angiogenesis-related diseases; it can overcome poor delivery and the problem of drug resistance. Further, it could provide a new avenue for other angiogenic diseases, such as atherosclerosis, rheumatoid arthritis, diabetic retinopathy, psoriasis, endometriosis, and adiposity.

In addition, the potential use of AgNPs for cancer diagnosis and treatment is immense; to address this issue, a variety of modalities have been developed. Although various methods are available, the synergistic effects of AgNPs and antibiotics on antibacterial agents or multiple therapeutic agents on anti-cancer activity/tumor reduction are still obscure. Therefore, more studies are required to explain the synergistic effect of the two different cytotoxic agents at a single time point. These kinds of studies could provide understanding, mechanisms, and efficiency of the synergistic effect of two different agents or multiple agents; thus, they would help to develop a novel system bearing multiple components with synergistic effects for the treatment of various types of cancer. Although AgNPs have been focused on therapeutic purposes, further research is inevitable in animal models to confirm the mechanisms and to gain a comprehensive picture of biocompatibility vs. toxicity of AgNPs. Finally, if we succeed in all these studies, it would help the researchers of the nanoscience and nanotechnology community to develop safer, biocompatible, efficient cancer or anti-angiogenic agents containing AgNPs. Eventually, to ensure the biosafety of the use of AgNPs in humans, studies dealing with biocompatibility of AgNPs and their interaction with cells and tissues are inevitable. Finally, the great concern is that the developing nanotechnology-based therapy should be better than available technologies, and it should overcome the limitations of existing treatment techniques. Finally, it has to provide a safe, reliable, and viable treatment of diseases with high accuracy in a patient-friendly manner.

Acknowledgments

This paper was supported by the KU-Research Professor Program of Konkuk University. This work is also supported by the Science and Technology Research Program from the Department of Education of Hubei Province in China (D20151701). Although we are the authors of this review, we would never have been able to complete it without the great many people who have contributed to the field of nanoparticles research particularly silver nanoparticles. We owe our gratitude to all those researchers who have made this review possible. We wish to thank all the investigators who have contributed to the field of synthesis, characterization, biomedical application and therapeutic approaches of silver nanoparticles. We have cited as many references as permitted, and apologize to the authors of those publications that we have not cited due to limitation of references. We apologize to other authors who have worked on the several aspects of AgNPs, but whom we have unintentionally overlooked.

Author Contributions

Sangiliyandi Gurunathan came up with the idea and participated in writing of the manuscript. Xi-Feng Zhang performed all literature surveys. Wei shen and Zhi-Guo Liu analyzed the interpretation of literature. All authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

• Open access
• Published: 03 May 2021

Green synthesized plant-based silver nanoparticles: therapeutic prospective for anticancer and antiviral activity

• Nancy Jain 1 ,
• Priyanshu Jain 1 ,
• Devyani Rajput 1 &
• Umesh Kumar Patil   ORCID: orcid.org/0000-0002-2096-9922 1  

Micro and Nano Systems Letters volume  9 , Article number:  5 ( 2021 ) Cite this article

18k Accesses

89 Citations

3 Altmetric

Metrics details

Nanotechnology holds an emerging domain of medical science as it can be utilized virtually in all areas. Phyto-constituents are valuable and encouraging candidates for synthesizing green silver nanoparticles (AgNPs) which possess great potentials toward chronic diseases. This review gives an overview of the Green approach of AgNPs synthesis and its characterization. The present review further explores the potentials of Phyto-based AgNPs toward anticancer and antiviral activity including its probable mechanism of action. Green synthesized AgNPs prepared by numerous medicinal plants extract are critically reviewed for cancer and viral infection. Thus, this article mainly highlights green synthesized Phyto-based AgNPs with their potential applications for cancer and viral infection including mechanism of action and therapeutic future prospective in a single window.

Green approach of silver nanoparticle synthesis using Phyto-constituents is reviewed.

Characterization methods of silver nanoparticles are discussed.

Potential for anticancer and antiviral activities of Phyto-based silver nanoparticles including mode of action are highlighted.

Therapeutic prospective and future challenges are summarized.

Introduction

Advancement in the field of medical science is uplifted by the development of nanotechnology which provides tremendous solutions to deal with life-threatening diseases. The nanotechnology is a huge milestone which have various applications in many sectors like electronics [ 1 ], textiles [ 2 ] and most importantly in healthcare as targeted drug delivery, diagnosis, treatment, biosensing for the welfare of mankind [ 3 ]. Nanoparticles present a highly attractive platform for a diverse array of biological applications. Nanoparticles are more targeted treatments for difficult to manage diseases such as cancers.

The biggest challenge in the treatment of cancer is to prevent non-cancerous cells from destruction while damaging the tumor cells. Current mode of treatment, either oral or parenteral, circulate in the entire body and cause harm [ 4 ]. Targeted drug therapies using nanosized formulations can be a useful approach to rectify this problem and only the proliferating cancerous cells will be targeted for cytotoxicity. Nanosized formulations are truly remarkable gift for the treatment of chronic disease such as cancer [ 5 ].

The viral disease which is the cause of today’s pandemic has grown the terror to mankind and ruining the world. Millions of people lost their lives globally, while others lost their families, people lost employment, children lost their proper way of education, and this all leads to economic crises worldwide. Corona virus the ultimate villain of this epidemic [ 6 ]. Not only coronavirus but other viruses also develop and spread widely and cause life-threatening diseases like- HIV, Herpesvirus, Influenza virus, Hantavirus, Ebolavirus, Nipah virus [ 7 ]. All pharmaceutical companies and researchers are engaged to develop vaccines against the virus. Nevertheless, the world can’t get over it. This alarms urgent research and development of the new antiviral drug to cure the human health of life-threatening viruses.

Metallic nanoparticles are attacking much attention because of their unique properties and use. Nanoparticles of silver metal are the most extensively studied as it offers tremendous broad-spectrum activities. Research on AgNPs has made giant strides in nanoscience especially as antimicrobial, antibacterial [ 8 , 9 ], antioxidants [ 10 ], antifungal [ 11 ], anti-inflammatory [ 12 ], anticancer [ 13 ], anti-angiogenic [ 14 ], AgNPs are small in the size range of 10–100 nm with unique Physico-chemical properties (size, shape, optical activity, electric conductivity, high surface area). Plant mediated AgNPs are safe, eco-friendly, cost-effective, rapidly synthesized at the same time they play a vital role as reducing, stabilizing, and capping agents. Thus, the green method of synthesizing AgNPs offers numerous advantages over chemical and physical methods.

Silver nanoparticles are one of the most vital and fascinating nanomaterials among several metallic nanoparticles that are involved in biomedical applications [ 4 , 5 ]. Silver nanoparticles have attracted increasing attention for the wide range of application in biomedicine. They are used as antimicrobial agents in wound dressings, as topical creams to prevent wound infection and as anticancer agents [ 8 ]. Nano sized metallic particles are unique and can considerably change physical, chemical and biological properties due to their surface to volume ratio, therefore these nanoparticles have been exploited for various purposes [ 3 ]. Green synthesized nanoparticles show high yield, solubility and high stability. Among several synthetic methods for AgNPs biological methods seems to be simple, rapid, non-toxic, dependable and green approaches than can produce well-defined size and morphology under optimized conditions for traditional research [ 5 , 7 ].

This article is an attempt to expose greenly synthesized AgNPs overviewing their methods of characterization and application in the field of bioscience. Considering the literature in this regard, anticancer and antiviral activities of AgNPs are described with their possible mechanism of action on different cell lines. Before concluding the article, important therapeutic and future challenges of AgNPs regarding anticancer and antiviral activity were discussed.

• Green synthesis

Green synthesis is the biological method of synthesizing nanoparticles. Green synthesis of AgNPs is the most accepted method as it provides various advantages over conventional techniques (chemical and physical methods). The technique is eco-friendly, easy, no sophisticated instruments and chemicals are required. No toxic chemicals are involved as reducing agents and stabilizing agents are derived from plants [ 15 ]. Plants provide free reducing, stabilizing, and capping agent and also cost of microorganism and culture media is reduced. Ultimately reducing the overall cost of the formulation [ 16 , 17 ]. This method is a good alternative to conventional methods of nanoparticles synthesis. The product formed using this method is more stable with the desired shape and size [ 18 , 19 ].

Naturally occurring phytoconstituents consist of numerous primary and secondary metabolites such as proteins, amino acid, vitamins, nucleic acids and alkaloids, terpenoids, flavonoids, saponins, phenols respectively [ 20 ]. These primary and secondary metabolites in plant extract act as reducing agents for silver ions by getting oxidized and coats the newly developed particles. In the presence of oxygen, such as in silver nitrate (AgNO 3 ), these metabolites lose their electron and become oxidized via common cellular procedures, thus act as reducing agents [ 21 , 22 ] (Fig. 1 ).

Synthesis of AgNPs through Green synthesis method

The process of green synthesis begins when the plant extract is mixed with silver nitrate solution. Over a certain period of time, the change in the color indicates the formation of nanoparticles. Silver nitrate solution which has positive ions (Ag +) converts to zero-valent state (Ag° species) when plant extract or active constituents from plants are added to it, which acts as a reducing agent. Then the nucleation process begins which is followed by the immediate growth phase. This leads to join smaller particles to form larger nanoparticles which are more stable thermodynamically. Finally, different shapes of nanoparticles are formed like cubes, spheres, triangles, hexagons, pentagons, rods, and wires. Several factors that affect the synthesis and formation of nanoparticles are pH, temperature, the concentration of plant extract, reaction time, the concentration of silver nitrate, pressure, and others [ 23 , 24 ].

Phytoconstituent of the plant act as an excellent reducing and stabilizing agent. The flower extract of  Lonicera   hypoglauca  flower act as reducing and capping agents in the synthesis of AgNPs and possesses anticancer activity [ 25 ].  Artocarpus integer  leaf extract was used to synthesize AgNPs and formed the spherical NPs of 5.76 nm to 19.1 nm [ 26 ].  Catharanthus   roseus  extract used to synthesize AgNPs showed the presence of alkaloid of indole type which acts as a reducing and stabilizing agent [ 10 ]. Greenly synthesized AgNPs using leaf extract of  Clitoria ternatea  and  Solanum   nigrum  showed antibacterial activity against nosocomial pathogens. The synthesis of nanoparticles was confirmed by UV, FTIR, SEM, and XRD [ 27 ]. Abelmoschus esculentus  (L.) pulp extract was incorporated to form AgNPs of 3-11nm and showed anticancer and antimicrobial activity [ 28 ]. Besides these, several other types of research show well-developed nanoparticles using the green synthesis method and their potential role in medicine.

Characterization of plant-based silver nanoparticles-

Different factors modulate the characteristics of AgNPs like shape, size, crystallinity, surface charge, surface coating, and biological activity. There are several technologies available to study the characters and properties of nanoparticles such as Ultra-violet visible spectroscopy (UV-vis), X-ray diffraction (XRD), Fourier Transform Infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), Transmission electron microscope (TEM), Dynamic light scattering (DLS), Atomic Force Microscopy (AFM) (Fig. 2 ).

AgNPs with their Characterization Methods

UV–vis spectroscopy

UV-Vis spectroscopy is the simple, effective, and primary characterization technique used to determine the stability, optical properties, and the synthesis reaction conditions such as time, temperature, and pH [ 29 ]. The free-electron oscillates and produces charges over the surface of nanoparticles under electromagnetic radiations as a result of the SPR effect [ 20 ]. The process of AgNPs synthesis is the coloured reaction and shows strong and sharp absorption bands under the visible region in the range of 400–500 nm [ 30 ]. Curcumin loaded AgNPs synthesized with different concentration of pure curcumin as 0.005 g (C0), 0.1g (C1), and 0.25g (C2) showed absorbance spectra at 427 nm, 428 nm, and 445 nm for C0, C1, C2 respectively [ 31 ]. Salvia spinosa grown extract loaded green synthesized nanoparticles has shown broad bell-shaped spectrum curve in UV-Vis analysis [ 32 ]. Similarly, the change in the color of the reaction and reduced silver ions can and has been measured using UV-Vis spectroscopy in many studies [ 33 , 34 , 35 , 36 ].

X-Ray diffraction (XRD)

XRD is a characterization methodology for measuring the crystallinity of the AgNPs. X-rays strike the crystal surface and interact with the atoms. The atoms arrange themselves at a proper distance on the crystalline plane and show a pattern of diffraction [ 20 , 30 ]. XRD characterization method is been used in different researches to determine the crystallinity of green synthesized AgNPs. AgNPs prepared using aqueous leaf extract of Urtica dioica Lin resulted crystalline structure by showing average particle size ~25 nm. The sample show strong reflection at 38.45°, 46.35°, 64.75°, and 78.05° that attributes to 111, 200, 220, and 311crystalline plane [ 37 ]. Similarly, XRD pattern of AgNPs prepared using Pedalium murex leaf extract showed peaks at 38.19°, 44.37°, 64.56° and 77.47° attributes to the crystalline plane of 111, 200, 220, and 311 with average size of 14nm [ 38 ]. The XRD pattern obtained from the silver nanoparticles synthesized using the leaf extract of Clitoria ternatea has shown intense peak at 28, 33, 38, 44, 46, 55, 58, 65 and 77 and silver nanoparticles synthesized using the leaf extract of Solanum nigrum has peak at 28, 32, 39, 45, 55, 57, 65, 69, 75 and 77 which are induced as crystalline silver [ 27 ].

Fourier transform infrared (FTIR) spectroscopy

FTIR is a highly reliable analytical method that detects and displays elements, chemical structure, chemical bonds, functional groups, and bonding arrangements of molecules [ 9 , 39 ]. AgNPs characterization through FTIR is done to identify the molecules which act as coating and stabilizing agents and also to detect the reduction of silver ions [ 20 ]. The FTIR spectra shows that amide and carboxylic functional groups may be responsible for the reduction or capping in the green synthesis of AgNPs [ 30 ]. Greenly synthesized AgNPs using leaf extract of Catharanthus roseus shows major peaks at 2401, 2073, 1706, 1084, and 8208 cm -1 which indicates the presence of different functional groups such as carboxylic acid group (O-H), Alkynes group (RC=CH), ketone group (C=O), Alcohol and amide groups, and phenyl ring, primary and secondary amine (N-H) group respectively [ 9 ]. Tectona grandis seeds extract loaded greenly synthesized nanoparticles FTIR spectrum showed bands at 1745, 1643, 1508 and 1038 cm-1 were assigned to stretching vibration of C=O bond of carboxylic acid or ester, N-C=O amide bond of proteins, nitro compounds, C-N amine bond respectively [ 40 ].

Electron microscopy

Electron microscopy is the high-resolution microscopy and the most accepted method to determine the morphology of the nanoparticles. This includes scanning electron microscopy (SEM) and Transmission Electron microscopy (TEM). The greenly synthesized AgNPs can be visualized when the electron beam strikes the nanostructured particles. Structural characterization of AgNPs using electron microscopy provides qualitative and quantitative information regarding the size, shape, size distribution, dry diameter distribution [ 20 , 30 ].

Scanning electron microscopy (SEM)

SEM visualize the surface morphology of the sample. The image is obtained when the electron is reflected from the surface of the sample [ 20 ]. The high-resolution image of the surface of nanoparticles which enrich us with valuable information like size, shape, topography, composition, electrical conductivity, and other properties [ 30 ]. There are many examples of greenly synthesized AgNPs characterized by SEM. SEM analysis of Acetyl-11-keto-β-boswellic acid mediated AgNPs (AKBA-AgNPs) showed spherical shape AgNPs with size range of 6–70 nm [ 41 ]. Similarly, AgNPs prepared using root extract of Glycyrrhiza glabra and leaf extract of Artemisia turcomanica showed particles diameter as 20–30 nm and 21.22 nm respectively [ 17 , 42 ]. FESEM of Tectona grandis seeds extract loaded silver nanoparticles shows the presence of oval, spherical shape nanoparticles. The AgNPs were in the range of 10–30 nm and confirms the face centred cubic (fcc) crystalline structure of metallic silver [ 40 ].

Transmission electron microscopy (TEM)

TEM provides the direct visualizes of the image which is obtained from the transmitted electron. It gives the structural and chemical behavior of the nanoparticles at a high electron beam with high resolution [ 20 ]. Greenly synthesized AgNPs have been characterized and visualized using TEM by many researchers. AgNPs prepared using leaf extracts of Viburnum lantana, Couroupita guianensis, and Malachra capitata resulted in size range of 20–70 nm, 25–40 nm, 30–35 nm respectively and possess predominantly spherical shape [ 43 , 44 , 45 ]. Lysiloma acapulunsis extract loaded silver nanoparticles TEM analysis showed the crystalline structure with visible lattice fringes [ 46 ]. The photographic image is formed when the sample and the high-intensity electron beam interact with each other. It is the most accepted technique to study the formation of AgNPs by directly visualizing the image of the nanoparticles. It has a unique ability to detect the core structure, diameter, size, shape, etc. [ 30 ].

Atomic force microscopy (AFM)

AFM is also used for the analysis of the size, surface morphology, mechano-structural and physical properties by phosphorus-doped silicon probe [ 20 ]. For characterization, the sample of AgNPs is prepared by dissolving in water or ethanol and the droplet is applied to the silicon substrate and allowed to dry. After drying, AFM analysis of the silicon-substrate which consists of the sample on it is done using a probe [ 30 ]. Tamoxifen-loaded AgNPs on AFM studies showed average size range 17.5 ± 2.5 nm [ 47 ].

Dynamic light scattering (DLS)

DLS provides the diameter of particles present in the formulation which are dispersed in the liquid. It determines the size of the AgNPs colloidal suspension. DLS is based on the principle of scattering of light. DLS is been used widely for the characterization of AgNPs which are synthesized using phytoconstituents [ 38 , 48 ]. The dispersed particles in the colloidal suspension scatter the light and as a result the image of the particles is obtained and size distribution can be determined in the range of 0.3–10 µm [ 20 ]. Pedalium murex leaf extract mediated AgNPs showed the average particle size distribution of 73.14  nm [ 38 ]. Similarly, AgNPs synthesized using Salvia miltiorrhiza extract showed the particle size 128 nm [ 49 ].

Zeta potential analysis

Zeta potential analysis is usually done to determine the surface charge and stability of the formulation. By this analysis, one can evaluate the colloidal stability of the greenly synthesized AgNPs by quantifying the velocity of the nano-sized particles. Under the influence of the electric field, the velocity of the particles is evaluated at which they travel towards the electrodes [ 20 ]. AgNPs synthesized using seed extract of Nigella sativa and leaf extracts of Gloriosa superba and Cynara scolymus showed that particles possess negative charge with the potential of − 18.8 ± 0.372, − 27.0, and − 32.3 ± 0.8 mV respectively [ 50 , 51 , 52 ]. Zeta potential of the Phyla dulcis extract loaded silver nanoparticles was analyzed and values were between − 20 and − 24 mV indicated that the AgNPs are relatively stable [ 53 ].

Plant- based silver nanoparticles for cancer

Cancerous cells evade apoptosis or programmed cell death and continue to proliferate. The aforementioned is the hallmark of cancer cells and the major focus of cancer therapy development. Plant-based nanosized silver is emerging to tackle cancer effectively. Two signally pathways i.e. intrinsic pathway and extrinsic pathway that exist for the activation of programmed cell death or Apoptosis. DNA damage or severe cell stress triggers apoptosis which is depriving in cancerous cells. Greenly synthesized AgNP using a bioactive fraction of  Pinus roxburghii  were reported to possess cytotoxic activity against lungs and prostate cancer cells. Apoptosis was examined to be induced through the intrinsic pathway via mitochondrial depolarization and DNA damage. An increase in ROS, cell cycle arrest, and caspase-3 activation also leads to apoptosis of cancer cells [ 54 ]. AgNPs synthesized utilizing  Phyllanthus emblica  leaf extract showed anticancer activity against Hepatocellular carcinoma (HCC) [ 55 ]. AgNP-dipalmitoyl-phosphatidylcholine composites forming liposomes (Lipo-AgNP) were found cytotoxic by inducing ROS formation and DNA damage. Activation of proapoptotic protein Bax and inhibition of Bcl-2 protein leads to the release of cytochrome C and gradually activates caspase causing apoptosis in macrophages [ 56 ].

Biosynthesized AgNPs using phycocyanin reported antimicrobial and anticancer activity. Cytotoxic action was investigated against breast cancer cell line and Ehrlich ascites carcinoma bearing mice (IC50 − 27.79 ± 2.3 µg/mL) [ 57 ]. AgNPs of two size- 2 nm and 15 nm, were investigated for anticancer activity against MCF-7 and T-47D cells and determined to induce Endoplasmic reticulum stress via unfolded protein response (UPR) and also enhances activation of caspase 9 and caspase 7 causing cell death [ 58 ]. AgNPs are also confirmed to exhibit strong cytotoxic by arrest cell cycle at the G2/M phase. In an investigation on A549 lung epithelial cells, it is reported that AgNPs strongly downregulates protein kinase-C (PKCζ) which leads to the capitulation of the cell cycle at the G2/M phase. AgNPs are further involved in the upregulation of P-53 protein, Bax and Bid, caspase-3, generation of ROS, and downregulating antiapoptotic protein-Bcl-2 and Bcl-w [ 59 ].  Cynara scolymus  also recognized as Artichoke, were employed to synthesize AgNPs and further research for anti-tumor activity with photodynamic therapy revealed that AgNPs modulates mitochondrial apoptosis via generation of ROS, regulates the apoptotic proteins and cause MCF7 breast cancer cells death [ 52 ]. Similarly,  Moringa oleifera [ 60 ],  Tropaeolum majus [ 61 ],  Punica granatum  [ 62 ],  Gloriosa superba [ 51 ],  Teucrium polium  [ 63 ] plant extract used to synthesize AgNPs and reported to be cytotoxic against cancer cell lines. There are numerous related investigations and research that evidence that AgNPs are the potent and effective candidate for cancer therapy. The target cancer treatment is also possible using AgNPs.

Mechanism of action

The process of apoptosis starts with several stages of apoptotic protein activation, DNA damage, mitochondrial degradation, the formation of Apoptosome, and ultimately cell shrinkage. These become the major important targets to be utilized in cancer therapy. Silver nanoparticle acts on certain target areas and shows anticancer activity.

Recent researches state that AgNPs majorly works by enhancing Reactive oxygen species (ROS), increasing oxidative stress, and DNA destruction. ROS maintains the normal cellular homeostasis which is crucial for cell survival. ROS involves in the cellular transduction signaling pathways and forms as a free-radical by-product from cellular metabolism [ 64 ]. An extreme amount of intracellular ROS cause DNA, lipid, protein damage as a mechanism for AgNPs induced toxicity [ 28 , 65 , 66 ]. One of the studies reveals that through reverse transcription-polymerase chain reaction (RTq-PCR) techniques pro-apoptotic gene upregulation in AgNPs treated HCT-116 cells [ 67 ]. In the process of apoptosis caspase enzymes play an important role. Up-regulation in the expression of caspase 3, caspase 8, and caspase 9 excessively increase the induction of apoptosis. AgNPs treatment to HCT-116 cells exposed up-regulation of pro-apoptotic enzymes- caspase3, 8 and 9, and also PUMA (mediator of apoptosis linked to p53) resulting to induce apoptosis [ 67 , 68 ]. P53 is the protein mediator that controls and regulates stress signals related to apoptosis and cell cycle arrest [ 68 ]. AgNPs treatment on A549 lung epithelial cells indicates the up-regulation of p53 which leads to the arrest of the cell cycle at the G0-G1 phase and stops the cell division [ 59 , 69 ]

Green synthesized AgNPs using  Coptis chinensis  describes the mechanism of action as AgNPs increase the expression of pro-apoptotic proteins- Bax and Bak and decrease anti-apoptotic Bcl-2 and Bcl-XL protein [ 70 ]. B-cell lymphoma-2 (Bcl2) protein is a family of pro-apoptotic protein and anti-apoptotic protein, which are involved in the regulation of apoptosis. The pro-apoptotic proteins are- Bax and Bak, which initiate and stimulate the process of apoptosis. In the class of anti-apoptotic protein include- Bcl-2 and Bcl-XL protein, which are involved in the suppression of apoptosis [ 71 , 72 ].

Vascular endothelial growth factor (VEGF) causes angiogenesis which can proliferate the tumor cells and can transform the tumor from benign to a malignant state. Angiogenesis is the formation of the new blood vessel from the existing blood vessels. This is promoted by VEGF, which acts as a pro-angiogenic factor via VEGF-2 receptor (tyrosine kinases) [ 73 , 74 ]. The mechanism of action of AgNPs is extensively elaborated in an investigation that reveals VEGF-induced proliferation by angiogenesis is suppressed by AgNPs. AgNPs are considered as the potent anti-angiogenic agent that inhibits VEFG [ 14 , 74 ]. AgNPs activate apoptosis through cellular damages, anti-angiogenic pathway, and caspase cascade pathway. Schematic mechanism of action of AgNPs for anticancer activity is depicted in Fig. 3 . Various Plant-based Silver Nanoparticles have been developed for various anticancer activity. Their mechanism of action and other findings including cell model used for evaluation are summarised in Table 1 .

(1) AgNPs upregulates caspase-8 which leads to stimulate and activate pro-apoptotic proteins- Bid, tBid, and further increase the release of cytochrome C from mitochondria which activates Apaf-1, then forms Apoptosome. Following the formation of Apoptosome, caspases are activated and result in apoptosis. AgNPs also directly upregulates cleaved caspase-3 to increase the process of apoptosis. (2) AgNPs results in mitochondrial apoptosis by increasing the permeability of the mitochondrial membrane and reducing the production of ATP. AgNPs also upregulates the apoptotic protein- Bak and Bax, which increase the release of cytochrome C and induce apoptosis. (3) AgNPs acts on genetic material DNA and causes damages by the increasing generation of ROS that causes oxidative stress and damages the DNA. These nanoparticles inhibit the protein kinases (PKC) and cause cell cycle arrest at the G2/M phase. AgNPs upregulates P-23 Protein which is responsible to activate the apoptosis process by activating other pro-apoptotic protein. Following the DNA damage intracellular pro-apoptotic proteins are released to activate caspases and cause cell death. (4) Vascular endothelial growth factor (VEGF), which is the pro-angiogenic factor involved in the activation of signaling pathways that promotes cell proliferation and migration through tyrosine kinase receptor (VEGFR2) and cause angiogenesis in tumor cells. This mechanism is inhibited by AgNPs by suppressing VEGF induced cell proliferation

Plant-based silver nanoparticles for viral-infection

The viral infection is a complicated infection to treatment as a virus multiply and spread quickly. Various emerging life-threatening viruses already exist overpowering humans which involve coronavirus, Ebola virus, dengue virus, HIV, Influence virus. There is an increase in studies on AgNPs as an efficacious antiviral agent. The mode of antiviral action of AgNPs, as described in various studies could be- intracellular by blocking viral replication or extracellular by interacting with viral protein (gp120) and blocking the entry which could be different for a different type of virus (Fig. 4 ). AgNPs are considered to the potent and novel pharmacological agent possessing effective antiviral activity against feline coronavirus (FCoV) [ 105 ], Influenza virus [ 106 ], HIV [ 107 ], Adenovirus [ 108 ], Herpes simplex virus [ 109 ], Dengue virus [ 110 , 111 ], Chikungunya virus [ 112 ], Norovirus [ 113 ], bovine Herpesvirus [ 114 ], Human parainfluenza virus type 3 [ 115 ].

(1) AgNPs interact with the viral surface protein (gp120) in enveloped and unenveloped virus. (2) AgNPs blocks the penetration of virus into the host cell. (3) AgNPs blocks the cellular viral entry to Nucleus. (4) AgNPs inhibits the viral replication by blocking viral genome

Mode of action of AgNPs as viricidal in HIV-1, is described as AgNPs targets the gp120 and inhibits binding to host cell membrane. This leads to blocking entry, fusion, and infectivity [ 116 ]. The schematic mechanism of action of AgNPs for antiviral activity is depicted in Fig. 4 . AgNPs interferes with the Viral replication and inhibits the release of new virus progenies at non-toxic dose 10–25 µg/ml in the size range of 10nm in a study against Tacaribe virus (new world arenavirus) [ 117 ]. The envelope of the H3N3 influenza virus consists of two main glycoprotein- Hemagglutinin and Neuraminidase. AgNPs were tested for the inhibition of Hemagglutinin glycoprotein in an investigation. The hemagglutinin is the main protein that binds to the host membrane receptor. AgNPs inhibit Hemagglutinin through interfering with the disulfide bond present on the molecule and protect the host cell by inhibiting viral genome entry and fusion [ 118 ].

In an investigation against Herpes simplex virus type-1 (HSV-1), AgNPs capped with mercaptoethane sulfonate at 400 µg/ml completely block HSV-1 infection [ 119 ]. AgNPs also inhibit early phase replication of HSV-2 at a non-toxic concentration of 100 µg/ml in VERO cells. The study also revealed that at a low dose of 6.25 µg/ml, the AgNPs could inhibit the new progeny release and at a high dose of 100 µg/ml viral replication is inhibited. It was also suggested to coat Vero cells with polysaccharides to protect the cells from AgNPs cytotoxic effects [ 109 ]. Another study on herpes simplex virus and human parainfluenza virus type 3 using biologically synthesized AgNPs clarify that AgNPs interfere and decrease replication of virus depending upon the size and zeta potential of AgNPs [ 115 ].

The size-dependent interaction of AgNPs (1–10 nm) against the HIV-1 virus was investigated in research work. The study revealed that AgNPs act as viricidal against the virus by inhibiting the binding of the virus to host cells through interacting with gp120 protein of virus envelop [ 107 ]. AgNPs synthesized using marine actinomycetes possess antiviral activity against new castle viral disease. Nanoparticles of 1–10 nm size are said to interact with gp120 and may inhibit the binding of the virus to cells [ 120 ]. AgNPs loaded with curcumin were studied antiviral activity against Respiratory syncytial virus infection (RSV). Infected Hep-2 cells were treated with Curcumin loaded AgNPs showed inactivation of the virus. The study suggested that Curcumin loaded AgNPs inhibits the entry of RSV into the Hep-2 cells i.e. blocks the attachment [ 121 ]. The study of AgNPs coated magnetic hybrid colloid, against Bacteriophage fX174, murine norovirus (MNV), adenovirus serotype-2 (AdV-2) describes that the fore-mentioned complex showed interaction with the viral surface and might damage viral protein [ 122 ]. Similarly, AgNPs-chitosan composites antiviral activity against the influenza virus [ 123 ]. Various Plant-based Silver Nanoparticles have been developed for antiviral activity. Their mechanism of action and other findings including cell model used for evaluation are summarised in Table 2 .

Therapeutic and future challenges of plant-based silver nanoparticles

Green synthesized AgNPs are the emerging area of research with enormous potent activity. Plant-derived phytoconstituents used for green synthesis, are the numerous sources of potent drug providing excellent activity to fight and destroy the devastating diseases like cancer and viral infection. The size, shape, and surface charge of AgNPs have a direct impact on their biological activity. Thus, complete profiling of pharmacodynamics and pharmacokinetics is needed to understand the exact mechanism, distribution, toxicity, and side-effects. Some limited controlled studies suggested the toxicity of AgNPs in macrophage immune cells, but there is a vast difference between in vitro and in vivo condition [ 143 , 144 ].

After reviewing recent studies on AgNPs regarding cancer and viral infection leads to indicate some issues and limitations. (a) Detection of specific targets that AgNPs targets to kill the cancer cells to produce a targeted drug delivery system of AgNPs. (b) Identification of specific viruses against which AgNPs are efficiently potent. (c) Detection of specific combinations with which AgNPs show maximum potency for cancer and virus infection therapy. (d) Extensive studies are needed in vivo to develop clinically used AgNPs as a dosage form to treat the chronic disease like cancer. (e) The exact mechanism involved in the synthesis of green AgNPs is needed to be cleared. (f) Detailed studies on the toxicity of AgNPs in vivo is to be examined well.

Further many approaches can be utilized to increase the potency of nanoparticle of silver as by combining or hybridization. Magnetic hybrid colloid coated on AgNPs showed excellent results against specific viruses by inhibiting viral protein [ 122 ]. Viral infections whose mechanism is very typical to understand can be overpowered by using nano-sized particles. Several approaches to improve anticancer activity can also be made in nano-scale silver. Recently, a patent filed by Vijayan S. and Jisha MS reporting the antitumor and antimicrobial activity of bio-synthesized AgNPs using Withania endophyte  Colletotrichum gloeosporioides  conjugated with chitosan (patent publication number-2011841032445). Likewise, further work is necessary to achieve the optimum know how and understanding of AgNPs for different potent activity. AgNPs are prominent and can prove to be the boon in the field of nanotechnology by which excellent, effective, efficient and very potent nanoproduct can be formulated to treat the giant disease like cancer.

This review comprises the therapeutic prospective of green synthesized AgNPs in the treatment of cancer and viral infections. Here, we first gave an overview of the green synthesis of AgNPs, then reviewed the applications of AgNPs in the treatment of cancer and their possible mechanism for cytotoxic activities. Further Phyto-based AgNPs with antiviral activity with their possible mechanism were discussed. Finally, some therapeutic and future challenges were summarized. Plant-based AgNPs have resulted in excellent biological activity with less toxicity to normal cells and highly toxic to cancerous cells. This makes the AgNPs as a promising candidate for future cancer treatment. AgNPs have also reported dominating activity against various life-threatening viruses that make them suitable for viral infection therapy.

Although various studies on size, shape, capping agenting, reducing agents of AgNPs have been performed, nevertheless there is still no clear optimum condition indicated for proper synthesis and development of target drug delivery system for cancer; thus, extensive studies are required in this field. In addition to this, long-term studies of AgNPs in vivo are necessary to evaluate the toxicity and performance.

Availability of data and materials

Data sharing is not applicable to this article.

Balantrapu K, Goia DV (2009) Silver nanoparticles for printable electronics and biological applications. J Mat Res 24(09):2828–2836

Article   Google Scholar  

Hasan KMF, Pervez MN, Talukder ME, Sultana MZ, Mahmud S, Meraz MM, Bansal V, Genyang C (2019) A novel coloration of polyester fabric through green silver nanoparticles (G-AgNPs@PET). Nanomaterials 9:569

Burdusel AC, Gherasim O, Grumezescu AM, Mogoanta L, Ficai A, Andronescu E (2019) Biomedical applications of silver nanoparticles: an up-to-date overview. Mol 24:719

Google Scholar  

Karmous I, Pandey A, Ben K, Haj KB, Chaoui A (2020) Efficiency of the green synthesized nanoparticles as new tools in cancer therapy: insights on plant-based bioengineered nanoparticles, biophysical properties, and anticancer roles. Bio Tra Ele Res 196:330–342

Yesilot S, Aydin C (2019) Silver nanoparticles; a new hope in cancer therapy? East J Med 24(1):111–116

Siadati SA, Afzali M, Sayadi M (2020) Could silver nano-particles control the 2019-nCoV virus? An urgent glance to the past. Chem Rev Lett 3:9–11

Rai M, Deshmukh SD, Ingle AP, Gupta IR, Galdiero M, Galdiero S (2016) Metal nanoparticles: the protective nano-shield against virus infection. Crit Rev Microbiol 42(1):46–56

Sondi I, Sondi BS (2004) Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. J Col and Inter Sci 275:177–182

Nagarajan S, Kalaivani G, Poongothai E, Arul M, Natarajan H (2019) Characterization of silver nanoparticles synthesized from Catharanthus roseus ( Vinca rosea ) plant leaf extract and their antibacterial activity. IJRAR 6(1):680–685

Al-Shmgani HSA, Mohammed WH, Sulaiman GM, Saadoon AH (2017) Biosynthesis of Silver nanoparticles from Catharanthus roseus leaf extract and assessing their antioxidant, antimicrobial, and wound-healing activities. Art Cell Nanomed Biotech 45(6):1234–1240

Deya C, Bellotti N (2017) Biosynthesized silver nanoparticles to control fungal infections in indoor environments. Adv Nat Sci Nanosci Nanotechnol 8:1–8

Singh P, Ahn S, Kang JP, Veronika S, Huo Y, Singh H, Chokkaligam M, El-Agamy Farh M, Aceituno VC, Kim YJ, Yang DC (2018) In vitro anti-inflammatory activity of spherical silver nanoparticles and monodisperse hexagonal gold nanoparticles by fruit extract of Prunus serrulata : a green synthetic approach. Artific Cells Nanomed Biotechnol 46(8):2022–2032

Yuan YG, Zhang S, Hwang JY, Kong IK (2018) Silver nanoparticles potentiates cytotoxicity and apoptotic potential of camptothecin in human cervical cancer cells. Oxida Medi Cellu Longe 1:1–21

Kalishwaralal K, Banumathi E, Pandian SRK, Deepak V, Muniyandi J et al (2009) Silver nanoparticles inhibit VEGF induced cell proliferation and migration in bovine retinal endothelial cells. Coll and Surf B: Biointer 73:51–57

Nadaroglu H, Alayli GA, Ince S (2017) Synthesis of nanoparticles by green synthesis method. Int J Inno Res Rev 1(1):6–9

Herlekar M, Barve S, Kumar R (2014) Plant-mediated green synthesis of iron nanoparticles. J Nanoparti. 2014:1–9

Mousavi B, Tafvizi F, Bostanabad SZ (2018) Green synthesis of silver nanoparticles using Artemisia turcomanica leaf extract and the study of anti-cancer effect and apoptosis induction on gastric cancer cell line (AGS). Artifi Cells Nanomed Biotech 46(1):499–510

Thakur S, Mohan GK (2019) Green synthesis of silver nanoparticles of boswellic acid, and it’s in vitro anticancer activity. Int J Pharma Bio Sci 10(3):92–100

Bedlovicova Z, Salayova A (2017) Green-Synthesized Silver Nanoparticles and Their Potential for Antibacterial Applications. Bacterial Pathogenesis Antibacterial Control. 8:73–94

Silva LP, Pereira TM, Bonatto CC (2019) Frontiers and perspectives in the green synthesis of silver nanoparticles. Green Synth Characterizat Applicat Nanoparticles. 2019:137–164

Sanjay SS (2019) Safe nano is green nano. Green Synth Characterizat Applicat Nanoparticles 14:27–36

Ghosh S (2019) Green synthesis of nanoparticles and fungal infection. Green Synth Characterizat Applicat Nanoparticles 7:75–86

Roy A, Bulut O, Some S, Mandal AK, Yilmaz MD (2019) Green synthesis of silver nanoparticles: biomolecule-nanoparticle organizations targeting antimicrobial activity. RSC Adv 9:2673

Devatha CP, Thalla AK (2018) Green synthesis of nanomaterials. Synthe Inorganic Nanomater 31:169–184

Jang SJ, Yang IJ, Tettey CO, Kim KM, Shin HM (2016) In-vitro anticancer activity of green synthesized silver nanoparticles on MCF-7 human breast cancer cells. Mat Sci Engineer C 68:430–435

Majeed S, Bakhtiar NFB, Danish M, Mohamad Ibrahim MN, Hashim R (2019) Green approach for the biosynthesis of silver nanoparticles and its antibacterial and antitumor effect against osteoblast MG-63 and breast MCF-7 cancer cell lines. Sus Chem Pharma 12:100138

Krithiga N, Rajalakshmi N, Jayachitra A (2015) Green synthesis of silver nanoparticles using leaf extracts of Clitoria ternatea and Solanum nigrum and study of its antibacterial effect against common nosocomial pathogens. J Nanosci 2015:1–8

Mollick MMR, Rana D, Dash SK, Chattopadhyay S, Bhowmick B, Maitya D, Mondala D et al (2019) Studies on green synthesized silver nanoparticles using Abelmoschus esculentus (L.) pulp extract having anticancer (in vitro) and antimicrobial applications. Ara J Chem 12:2572–2584

Chen X, Jensen L (2016) Understanding the shape effect on the plasmonic response of small ligand coated nanoparticles. J Opt. 18:1–18

Noah N (2019) Green synthesis: characterization and application of silver and gold nanoparticles. Green Synth Characterizat Applicat Nanoparticles. 53:111–135

Khan MJ, Shameli K, Sazili AQ, Selamat J, Kumari S (2019) Rapid green synthesis and characterization of silver nanoparticles arbitrated by curcumin in an alkaline medium. Molecules 24:719

Pirtarighat S, Ghannadnia M, Baghshahi S (2019) Green synthesis of silver nanoparticles using the plant extract of Salvia spinosa grown in vitro and their antibacterial activity assessment. J Nanostruc Chemis 9:1–9

Gudikandula K, Maringanti SC (2016) Synthesis of silver nanoparticles by chemical and biological methods and their antimicrobial properties. J Exp Nanosci 11(9):714–721

Ahmed S, Saifullah Ahmad M, Swami BL, Ikram S (2016) Green synthesis of silver nanoparticles using Azadirachta indica aqueous leaf extract. J Rad Res App Sci 9:1–7

Osibe DA, Chiejina NV, Ogawa K, Aoyagi H (2018) Stable antibacterial silver nanoparticles produced with seed-derived callus extract of Catharanthus roseus . Art Cells Nanomed Biotech 46(6):1266–1273

Mukunthan KS, Elumalai EK, Patel TN, Murty RV (2011) Catharanthus roseus : a natural source for the synthesis of silver nanoparticles. Asian Pac J Trop Biomed 1(4):270–274

Jyoti K, Baunthiya M, Singh A (2016) Characterization of silver nanoparticles synthesized using Urtica dioica Linn. leaves and their synergistic effects with antibiotics. J Rad Res App Sci 9(3):217–227

Anandalakshmi K, Venugob J, Ramasamy V (2016) Characterization of silver nanoparticles by green synthesis method using Pedalium murex leaf extract and their antibacterial activity. App Nanosci 6:399–408

Baudot C, Tan CM, Kong JC (2010) FTIR spectroscopy as a tool for nano-material characterization. Infrared Phys Technol 53(6):434–438

Rautela A, Rani J, Das MD (2019) Green synthesis of silver nanoparticles from Tectona grandis seeds extract: characterization and mechanism of antimicrobial action on different microorganisms. J Ana Sci Tech 10:1–10

Khan A, Al-Harrasi A, Rehman NU, Sarwar R, Ahmad T, Ghaffar R, Khan H, Al-Amri I, Csuk R, Al-Rawahi A (2019) Loading AKBA on surface of silver nanoparticles to improve their sedative-hypnotic and anti-inflammatory efficacies. Nanomed. 14:1–16

Sivalingam D, Karthikeyan S, Arumugam P (2012) Biosynthesis of silver nanoparticles from Glycyrrhiza glabra root extract. Arch App Sci Res 4(1):178–187

Shafaghat A (2015) Synthesis and characterization of silver nanoparticles by photosynthesis method and their biological activity, synthesis and reactivity in inorganic. Metal-Org Nano-Met Chem 45(3):381–387

Devaraj P, Kumari P, Aarti C, Renganathan A (2013) Synthesis and characterization of silver nanoparticles using cannonball leaves and their cytotoxic activity against MCF-7 Cell Line. J Nanotech. 2013:1–5

Srirangam GM, Rao KP (2017) Synthesis and characterization of silver nanoparticles from the leaf extract of Malachra capitata (l). Ras J Chem 10(1):46–53

Garibo D, Borbon-Nunez HA, de Leon JND, Mendoza EG, Estrada I, Toledano-Magana Y, Tiznado H, Ovalle-Marroquin M, Soto-Ramos AG, Blanco A, Rodríguez JA (2020) Green synthesis of silver nanoparticles using Lysiloma acapulcensis exhibit high-antimicrobial activity. Scienti rep 10:1–11

Rasheed M, Ali A, Kanwal S, Ismail M, Sabir N, Amin F (2019) Synergy of green tea reduced tamoxifen-loaded silver nanoparticles exhibit OGT downregulation in breast cancer cell line. Dig J Nanomat Biostr 14(3):695–704

Gurunathan S, Qasim M, Park C, Yoo H, Kim IDJH, Hong K (2018) Cytotoxic potential and molecular pathway analysis of silver nanoparticles in human colon cancer cells HCT116. Int J Mol Sci 19:2269

Zhang K, Liu X, Samson OASR, Ramachandran AK, Ibrahim IAA, Nassir AM, Yao J (2019) Synthesis of silver nanoparticles (AgNPs) from leaf extract of Salvia miltiorrhiza and its anticancer potential in human prostate cancer LNCaP cell lines. Art Cells Nanomed Biotech 47(1):2846–2854

Usmani A, Mishra A, Jafri A, Arshad M, Siddiqui MA (2019) Green synthesis of silver nanocomposites of Nigella sativa seeds extract for hepatocellular carcinoma. Cur Nanomat 4(3):1–10

Muthukrishnan S, Vellingiri B, Murugesan G (2018) Anticancer effects of silver nanoparticles encapsulated by Gloriosa superba (L.) leaf extracts in DLA tumor cells. Fut J Pharma Sci 4:206–214

Erdogan O, Abbak M, Demirbolat GM, Birtekocak F, Aksel M, Pasa S et al (2019) Green synthesis of silver nanoparticles via Cynara scolymus leaf extracts: The characterization, anticancer potential with photodynamic therapy in MCF7 cells. PLoS ONE 14:6

Carson L, Bandara S, Joseph M, Green T, Grady T, Osuji G, Weerasooriya A, Ampim P, Woldesenbet S (2020) Green synthesis of silver nanoparticles with antimicrobial properties using Phyla dulcis plant extract. Foodbor patho dis 17:04–511

Kumari R, Saini AK, Kumar A, Saini RV (2020) Apoptosis induction in lung and prostate cancer cells through silver nanoparticles synthesized from Pinus roxburghii bioactive fraction. J Bio Inorg Chem 25:23–37

Singh D, Yadav E, Falls N, Kumar V, Singh M, Verma A (2019) Phyto-fabricated silver nanoparticles of Phyllanthus emblica attenuated diethyl-nitrosamine-induced hepatic cancer via knock-down oxidative stress and inflammation. Inflammopharmacol 27:1037–1054

Yusuf A, Casey A (2020) Liposomal encapsulation of silver nanoparticles (AgNP) improved nanoparticle uptake and induced redox imbalance to activate caspase-dependent apoptosis. Apo 25:20–134

El-Naggar NE, Hussein MH, El-Sawah AA (2017) Bio-fabrication of silver nanoparticles by phycocyanin, characterization, in vitro anticancer activity against breast cancer cell line and in vivo cytotoxicity. Scient Rep 7:1–20

Simard JC, Durocher I, Girard D (2016) Silver nanoparticles induce irremediable endoplasmic reticulum stress leading to unfolded protein response dependent apoptosis in breast cancer cells. Apo 21:1279–1290

Lee YS, Kim DW, Lee YH, Oh JH, Yoon S, Choi MS, Lee SK, Kim JW, Lee K, Song CW (2011) Silver nanoparticles induce apoptosis and G2/M arrest via PKC f -dependent signaling in A549 lung cells. Arch Toxicol 85:1529–1540

Vasanth K, Ilango K, Kumar MR, Agrawal A, Dubey GP (2014) Anticancer activity of Moringa oleifera mediated silver nanoparticles on human cervical carcinoma cells by apoptosis. Coll Surf B: Bioint 117:354–359

Valsalam S, Paul A, Arasu MV, Al-Dhabi NA, Mohammed Ghilan AK, Kaviyarasu K, Ravindran B, Chang SW, Arokiyaraj S (2018) Rapid biosynthesis and characterization of silver nanoparticles from the leaf extract of Tropaeolum majus L. and its enhanced in-vitro antibacterial, antifungal, antioxidant and anticancer properties. J Photochem Photobiol, B 191:65–74

Sarkar S, Kotteeswara V (2018) Green synthesis of silver nanoparticles from aqueous leaf extract of Pomegranate ( Punica granatum ) and their anticancer activity on human cervical cancer cells. Adv Nat Sci Nanosci Nanotechnol 9(2):025014

Hashemi F, Tasharrofi N, Saber MM (2020) Green synthesis of silver nanoparticles using Teucrium polium leaf extract and assessment of their antitumor effects against MNK45 human gastric cancer cell line. J Mol Str 1208:127889

Wang L, Xu J, Yan Y, Liu H, Karunakaran T, Li F (2019) Green synthesis of gold nanoparticles from Scutellaria barbata and its anticancer activity in pancreatic cancer cell (PANC-1). Art Cells Nanomed Biotech 47(1):1617–1627

Foldbjerg R, Dang AD, Autrup H (2011) Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol 85:743–750

Blanco J, Lafuente D, Gómez T, García T, Domingo JL, Sánchez DJ (2017) Polyvinyl pyrrolidone-coated silver nanoparticles in a human lung cancer cells: time-and dose-dependent influence over p53 and caspase-3 protein expression and epigenetic effects. Arch Toxicol 9:651–666

Kuppusamy P, Ichwan SJA, Al-Zikri PNH, Suriyah WH, Soundharrajan I, Govindan N, Yusoff MM, (2016) In Vitro Anticancer Activity of Au, Ag Nanoparticles Synthesized Using Commelina nudiflora L. Aqueous Extract Against HCT-116 Colon Cancer Cells. Bio Tr El Res 173(2):297–305

Karthik S, Sankar R, Varunkumar K, Ravikumar V (2014) Romidepsin induces cell cycle arrest, apoptosis, histone hyperacetylation and reduces matrix metalloproteinases 2 and 9 expression in bortezomib sensitized non-small cell lung cancer cells. Biomed Pharmacother 68(3):327–334

Nair APV, Sethu S, Lim HK, Balaji G, Valiyaveettil G, Hande MP (2012) Differential regulation of intracellular factors mediating cell cycle, DNA repair and inflammation following exposure to silver nanoparticles in human cells. Gen Int 3(1):1–14

Pei J, Fu B, Jiang L, Sun T (2019) Biosynthesis, characterization, and anticancer effect of plant-mediated silver nanoparticles using Coptis chinensis . Int J Nanomed 14:1969–1978

Jeng PS, Inoue-Yamauchi A, Hsieh JJ, Cheng EH (2018) BH3-dependent and independent activation of BAX and BAK in mitochondrial apoptosis. Cur Op Physio 3:71–81

Siddiqui WA, Ahad A, Ahsan H (2015) The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Archi Toxicol 89(3):289–317

Yang T, Yao Q, Cao F, Liu Q, Liu B, Wang XH (2016) Silver nanoparticles inhibit the function of hypoxia-inducible factor-1 and target genes: insight into the cytotoxicity and anti-angiogenesis. Int J Nanomed 11:6679–6692

Gurunathan S, Lee KJ, Kalishwaralal K, Sheikpranbabu S, Vaidyanathan R, Eom SH (2009) Antiangiogenic properties of silver nanoparticles. Biomaterial 30(31):6341–6350

Vivek R, Thangam R, Muthuchelian K, Gunasekaran P, Kaveri K, Kannan S (2012) Green biosynthesis of silver nanoparticles from Annona squamosa leaf extract and it’s in vitro cytotoxic effect on MCF-7 cells. Pro Biochem 47(12):2405–2410

Huo Y, Singh P, Kim YJ, Soshnikov V, Kang J, Markus J et al (2018) Biological synthesis of gold and silver chloride nanoparticles by Glycyrrhiza uralensis and invitro applications. Art Cell Nanomed Biotech 46(2):303–312

Khorrami S, Zarrabi A, Khaleghi M, Danaei M, Mozafari M (2018) Selective cytotoxicity of green synthesized silver nanoparticles against the McF-7 tumor cell line and their enhanced antioxidant and antimicrobial properties. Int J Nanomed 13:8013–8024

Jeyaraja A, Sathishkumara G, Sivanandhana G, MubarakAlid D, Rajesha M, Arun R et al (2013) Biogenic silver nanoparticles for cancer treatment: an experimental report. Col Sur Biointer 106:86–92

Kathiravan V, Ravi S, Ashok kumar S, (2014) Synthesis of silver nanoparticles from Melia dubia leaf extract and their in vitro anticancer activity. Spectro Acta Part A: Mol Biomol Spectro 130:116–121

Firdhouse MJ, Lalith P (2013) Biosynthesis of silver nanoparticles using the extract of Alternanthera sessilis —antiproliferative effect against prostate cancer cells. Cancer Nano 4:137–143

Mukundan D, Mohan kumar R, Vasanth kumari R (2015) Green synthesis of silver nanoparticles using leaves extract of Bauhinia Tomentosa linn and its invitro anticancer potential. Mater Today Proceed 2(9):4309–4316

Nilavukkarasia M, Vijayakumar S, Kumar SP (2020) Biological synthesis and characterization of silver nanoparticles with Capparis zeylanica L. leaf extract for potent antimicrobial and anti-proliferation efficiency. Mate Sci for Ene Techno 3:371–376

Vijayan R, Joseph S, Mathew B (2018) Indigofera tinctoria leaf extract mediated green synthesis of silver and gold nanoparticles and assessment of their anticancer, antimicrobial, antioxidant and catalytic properties. Art Cells Nanomed Biotech 46(4):861–871

Nayaka S, Chakraborty B, Pallavi SS, Bhat MP, Shashiraj KN, Ghasti B (2020) Synthesis of biogenic silver nanoparticles using Zanthoxylum rhetsa (Roxb) DC seed coat extract as reducing agent and in - vitro assessment of anticancer effect on A549 lung cancer cell line. Int J Pharma Res 12(3):302–314

Satsangi N (2020) Synthesis and characterization of biocompatible silver nanoparticles for anticancer application. J Inorg and Organometal Pol and Mat 30:1907–1914

Ali Abuderman A, Syed RA, Alyousef AS, Alqahtani M, Shamsul Ola M, Malik A (2019) Green synthesized silver Nanoparticles of Myrtus communis L (AgMC) extract inhibits cancer hallmarks via targeting aldose reductase (AR) and associated signaling network. PRO 7(11):860

Saratale RG, Benelli G, Kumar G, Kim DS, Saratale GD (2017) Bio-fabrication of silver nanoparticles using the leaf extract of an ancient herbal medicine, dandelion ( Taraxacum officinale ), evaluation of their antioxidant, anticancer potential, and antimicrobial activity against phytopathogens. Environ Sci Poll Res 25(11):10392–10406

Das S, Das J, Samadder A, Bhattacharyya SS, Das D, Khuda-Bukhsh AR (2013) Biosynthesized silver nanoparticles by ethanolic extracts of Phytolacca decandra, Gelsemium sempervirens, Hydrastis canadensis and Thuja occidentalis induce differential cytotoxicity through G2/M arrest in A375 cells. Col Sur B: Bioin 101:325–336

Dipankar C, Murugan S (2012) The green synthesis, characterization and evaluation of the biological activities of silver nanoparticles synthesized from Iresine herbstii leaf aqueous extracts. Col Sur: Biointer 98:112–119

Al-Sheddi ES, Farshori NN, Al-Oqail MM, Al-Massarani SM, Saquib Q, Wahab R et al (2018) Anticancer potential of green synthesized silver nanoparticles using extract of Nepeta deflersiana against human cervical cancer cells (HeLA). Bioinorg Chem App. 2018:1–12

Mahendran G, Kumari BDR (2016) Biological Activities of silver nanoparticles from Nothapodytes nimmonian (Graham) Mabb. Fruit extracts. F Sci and Hu Well 5:207–218

Islam NU, Amin R, Shahid M, Amin M, Zaib S, Iqbal I (2017) A multi-target therapeutic potential of Prunus domestica gum stabilized nanoparticles exhibited prospective anticancer, antibacterial, urease-inhibition, anti-inflammatory and analgesic properties. BMC Comp Alt Med 17:276

Prabhu D, Arulvasu C, Babu G, Manikandan R, Srinivasan P (2013) Biologically synthesized green silver nanoparticles from leaf extract of Vitex negundo L. induce growth-inhibitory effect on human colon cancer cell line HCT15. Pro Biochem 48(2):317–324

Hemlata Meena PR, Singh AP, Tejavath KK (2020) Biosynthesis of silver nanoparticles using Cucumis prophetarum aqueous leaf extract and their antibacterial and antiproliferative activity against cancer cell lines. ACS Omega 5:5520–5528

Sriranjani R, Srinithyaa S, Vellingiri V, Brindha P, Anthony SP, Sivasubramanian A, Muthuramana MS (2016) Silver nanoparticle synthesis using Clerodendrum phlomidis leaf extract and preliminary investigation of its antioxidant and anticancer activities. J Mol Li 220:926–930

Suwannakul S, Wacharanad S, Chaibenjawong P (2018) Rapid green synthesis of silver nanoparticles and evaluation of their properties for oral disease therapy. Sci Techno 40(4):831–839

Pandian S, Chidambaram S (2017) Antimicrobial, cytotoxicity and anti-cancer activity of silver nanoparticles from Glycyrrhiza glabra . IJPSR 8(4):1633–1641

Botcha S, Prattipati SD (2020) Callus extract mediated green synthesis of silver nanoparticles, their characterization and cytotoxicity evaluation against MDA-MB-231 and PC-3 Cells. Bio Nano Sci 10:11–22

Ahmed MJ, Murtaza G, Rashid F, Iqbal J (2019) Eco-friendly green synthesis of silver nanoparticles and their potential applications as antioxidant and anticancer agents. Drug Dev Ind Pharm 45(10):1682–1694

Sukirtha R, Priyanka KM, Antony JJ, Kamalakkannan S, Thangam R, Gunasekaran P, Achiraman S (2012) Cytotoxic effect of Green synthesized silver nanoparticles using Melia azedarach against in vitro HeLa cell lines and lymphoma mice model. Pro Biochem 47(2):273–279

Hemalatha KPJ, Shantakani S, Botcha S (2019) Green synthesis of silver nanoparticles using aqueous fruit and tuber extracts of Momordica cymbalaria . J Plant Biochem Biotech. 27:1–9

Chahardoli A, Karimi N, Fattahi A (2017) Biosynthesis, characterization, antimicrobial and cytotoxic effects of silver nanoparticles using Nigella arvensis seed extract. Ira J Pharma Res 16(3):1167–1175

Satpathy S, Patra A, Ahirwar B, Hussain MD (2018) Antioxidant and anticancer activities of green synthesized silver nanoparticles using aqueous extract of tubers of Pueraria tuberosa . Art Cell Nanomed Biotech 46(3):71–85

Young Ahn E, Jin H, Park Y (2019) Green synthesis and biological activities of silver nanoparticles prepared by Carpesium cernuum extract. Arch Pharm Res 42:926–934

Chen YN, Hsueh YH, Hsieh CT, Tzou DY, Chang PL (2016) Antiviral activity of graphene-silver nanocomposites against non-enveloped and enveloped viruses. Int J Environ Res 13(4):430

Kim M, Nguyen DY, Heo Y, Park KH, Paik HD, Kim YB (2020) Antiviral activity of Fritillaria thunbergii extract against Human Influenza Virus H1N1 (PR8) In Vitro, In Ovo and In Vivo. J Microbiol Biotechnol 30(2):172–177

Elechiguerra JL, Burt JL, Morones JR, Bragado BC, Gao X, Lara HH, Yacaman MJ (2005) Interaction of silver nanoparticles with HIV-1. J Nanobiotech 3(6):1–10

Chen N, Zheng Y, Yina J, Lia X, Zhenga C (2013) Inhibitory effects of silver nanoparticles against adenovirus type 3 in vitro. J Vir Met 193:470–477

Hu RL, Li SR, Kong FJ, Hou RJ, Guan XL, Guo F (2014) Inhibition effect of silver nanoparticles on herpes simplex virus 2. Gen Mol Res 13(3):7022–7028

Sujitha V, Murugan K, Paulpandi K, Panneerselvam C, Suresh U, Roni M, Nicoletti M et al (2015) Green-synthesized silver nanoparticles as a novel control tool against dengue virus (DEN-2) and its primary vector Aedes aegypti . Parasitol Res 114(9):3315–3325

Gaal H, Fouad H, Mao G, Tian J, Jianchu M (2017) Larvicidal and pupicidal evaluation of silver nanoparticles synthesized using Aquilaria sinensis and Pogostemon cablin essential oils against dengue and zika viruses’ vector Aedes albopictus mosquito and its histopathological analysis. Art Cell Nanomed Biotech 46(6):1171–1179

Sharma V, Kaushik S, Pandit P, Dhull D, Yadav JP, Kaushik S (2019) Green synthesis of silver nanoparticles from medicinal plants and evaluation of their antiviral potential against chikungunya virus. App Microbio Biotech 103:881–891

Bekele AZ, Gokulan K, Williams KM, Khare S (2016) Dose and size-AU2 c dependent antiviral effects of silver nanoparticles on feline calicivirus, a human norovirus surrogate. Foodbor Patho Dis 13(5):239–244

El-Mohamady RS, Ghattas TA, Zawrah MF, Abd El-Hafeiz YGM (2018) Inhibitory effect of silver nanoparticles on bovine herpesvirus-1. Int J Vet Sci Med 6:296–300

Gaikwad S, Ingle A, Gade A, Rai M, Falanga A, Incoronato N, Russo L, Galdiero S, Galdiero M (2013) Antiviral activity of myco-synthesized silver nanoparticles against herpes simplex virus and human parainfluenza virus type 3. Int J Nanomed 8:4303–4314

Lara HH, Ayala-Nuñez AV, Ixtepan-Turrent L, Rodriguez-Padill C (2010) Mode of antiviral action of silver nanoparticles against HIV-1. J Nanobiotech 8(1):1–10

Speshock JL, Murdock RC, Braydich-Stolle LK, Schrand AM, Hussain SM (2010) Interaction of silver nanoparticles with Tacaribe virus. J Nanobiotech 8(19):1–9

Xiang D, Zheng Y, Duan W, Li X, Yin J, Shigdar S, Liam M et al (2013) Inhibition of a/human/hubei/3/2005 (h3N2) influenza virus infection by silver nanoparticles in vitro and in vivo. Int J Nanomed 8:4103–4411

Baram-Pinto D, Shukla S, Perkas N, Gedanken A, Sarid R (2009) Inhibition of herpes simplex virus type 1 infection by silver nanoparticles capped with mercaptoethane sulfonate. Bioconjugate Chem 20:1497–1502

Avilala J, Golla N (2019) Antibacterial and antiviral properties of silver nanoparticles synthesized by marine actinomycetes. IJPSR 10(3):1–10

Yang XX, Li CM, Huang CZ (2016) Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection. Nanoscale 8(5):3040–3048

Park SJ, Park HH, Kim SY, Kim SJ, Woo K, Ko GP (2014) Antiviral properties of silver nanoparticles on a magnetic hybrid colloid. App Environ Microbio 80(8):2343–2350

Mori Y, Ono T, Miyahira Y, Nguyen VQ, Matsui T, Ishihara M (2013) Antiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza a virus. Nanosca Res Let 8(93):1–6

Dhanasezhian A, Srivani S, Govindaraju K, Parija P, Sasikala S, Kumar MRR (2019) Anti-Herpes Simplex Virus (HSV-1 and HSV-2) activity of biogenic gold and silver nanoparticles using seaweed Sargassum wightii . Ind J Geo Mar Sci 48:252–1257

Govindaraju K, Kiruthiga V, Kumar VG, Singaravelu G (2009) Extracellular synthesis of silver nanoparticles by a marine alga, Sargassum wightii grevilli and their antibacterial effects. J Nanosci Nanotech 9(9):5497–5501

Elbeshehy EKF, Elazzazy AM, Aggelis G (2015) Silver nanoparticles synthesis mediated by new isolates of Bacillus spp., nanoparticle characterization and their activity against Bean Yellow Mosaic Virus and human pathogens. Front Microbio 6(453):1–13

Tamilselvan S, Ak T, Kasivelu G (2017) Microscopy based studies on the interaction of bio-based silver nanoparticles with Bombyx mori Nuclear Polyhedrosis virus. J Virologic Met 6(16):1–22

Trefry JC, Wooley DP (2013) Silver nanoparticles inhibit vaccinia virus infection by preventing viral entry through a macropinocytosis-dependent mechanism. J Biomed Nanotech 9:1624–1635

Omara ST, Zawrah MF, Samy AA (2017) Minimum bactericidal concentration of chemically synthesized silver nanoparticles against pathogenic Salmonella and Shigella strains isolated from layer poultry farms. J App Pharma Sci 7(8):214–221

Dung TTN, Nam VN, Nhan TT, Ngoc TTB, Minh LQ, Nga BTT, Le VP, Quang DV (2020) Silver nanoparticles as potential antiviral agents against African swine fever virus. Mat Res Ex 6(12):1250g9

Morris D, Ansar M, Speshock J, Ivanciuc T, Qu Y, Casola A, Garofalo R (2019) Antiviral and immunomodulatory activity of silver nanoparticles in experimental RSV infection. Vir 11:732

Ochoa-Meza AR, Álvarez-Sánchez AR, Romo-Quiñonez CR, Barraza A, Magallón-Barajas FJ, Chávez-Sánchez A et al (2019) Silver nanoparticles enhance survival of white spot syndrome virus infected Penaeus vannamei shrimps by activation of its immunological system. Fish Shellfish Immuno 84:1083–1089

Park HH, Park S, Ko G, Woo K (2013) Magnetic hybrid colloids decorated with Ag nanoparticles bite away bacteria and chemisorb viruses. J Mat Chem B 1(21):2701

Quang HT, Thanh H, Thi N, Thuy Thanh N, Van Chung P, Hung Ngoc P (2017) Cytotoxicity and antiviral activity of electrochemical−synthesized silver nanoparticles against poliovirus. J Virologic Met 241:52–57

Fatima M, Zaidi NSS, Amraiz D, Afzal F (2016) In vitro antiviral activity of Cinnamomum cassia and its nanoparticles against H7N3 influenza a virus. J Microbiol Biotechnol 26(1):151–159

Sreekanth TVM, Nagajyothi PC, Muthuraman P, Enkhtaivan G, Vattikuti SVP, Tettey CO et al (2018) Ultra-sonication-assisted silver nanoparticles using Panax ginseng root extract and their anti-cancer and antiviral activities. J Photochem Photobio B Bio. 188:1–27

Haggag EG, Elshamy AM, Rabeh MA, Gabr NM, Salem M, Youssif KA, Samir S (2019) Antiviral potential of green synthesized silver nanoparticles of Lampranthus coccineus and Malephora lute . Int J Nanomed 14:6217–6229

Orlowski P, Kowalczyk A, Tomaszewska E, Ranoszek-Soliwoda K, We˛grzyn A, Grzesiak J, Celichowski G et al (2018) Antiviral activity of tannic acid modified silver nanoparticles: potential to activate immune response in herpes genitalis. Virus 10:524

Wan C, Tai J, Zhang J, Guo Y, Zhu Q, Ling D et al (2019) Silver nanoparticles selectively induce human oncogenic γ-herpesvirus-related cancer cell death through reactivating viral lytic replication. Cell Death Dis 10:392

Park SJ, Ko YS, Lee SJ, Lee C, Woo K, Ko GP (2018) Inactivation of influenza A virus via exposure to silver nanoparticle-decorated silica hybrid composites. Environ Sci Poll Res. 25:1–10

Xiang D, Chen Q, Pang L, Zheng C (2011) Inhibitory effects of Silver nanoparticles on H1N1 influenza A virus in vitro. J Virologic Met 178:137–142

Fayaz AM, Ao Z, Girilal M, Chen L, Xiao X, Kalaichelvan PT, Yao X (2012) Inactivation of microbial infectiousness by silver nanoparticles-coated condom: a new approach to inhibit HIV- and HSV-transmitted infection. Int J Nanomed 7:5007–5018

Ge L, Li Q, Wang M, Ouyang J, Li X, Xing MMQ (2014) Nanosilver particles in medical applications: synthesis, performance, and toxicity. Int J Nanomed 9:2399–2407

Park J, Lim DH, Lim HJ, Kwon T, Choi J, Jeong S, Choi I, Cheon J (2011) Size dependent macrophage responses and toxicological effects of Ag nanoparticles. Chem Commun 47:4382–4384

Download references

Acknowledgements

Authors are thankful to the Sophisticated Instrumentation Center (SIC), Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar for sophisticated instrumentation and other infrastructural facilities supported under DST-PURSE (II).

No specific grant received from any funding agency in the public, commercial or not for profit sectors.

Author information

Authors and affiliations.

Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, M.P., 470003, India

Nancy Jain, Priyanshu Jain, Devyani Rajput & Umesh Kumar Patil

You can also search for this author in PubMed   Google Scholar

Contributions

All the authors contributed for the study, compilation of data and preparation of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Umesh Kumar Patil .

Ethics declarations

Ethics approval and consent to participate.

Not applicable

Consent for publication

Competing interests.

The authors declare that they have no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Cite this article.

Jain, N., Jain, P., Rajput, D. et al. Green synthesized plant-based silver nanoparticles: therapeutic prospective for anticancer and antiviral activity. Micro and Nano Syst Lett 9 , 5 (2021). https://doi.org/10.1186/s40486-021-00131-6

Download citation

Received : 06 February 2021

Accepted : 19 April 2021

Published : 03 May 2021

DOI : https://doi.org/10.1186/s40486-021-00131-6

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Nanotechnology
• Silver nanoparticles
• Medicinal plants

Green synthesis of silver nanoparticles using plant extracts and their antimicrobial activities: a review of recent literature

First published on 13th January 2021

Synthesis of metal nanoparticles using plant extracts is one of the most simple, convenient, economical, and environmentally friendly methods that mitigate the involvement of toxic chemicals. Hence, in recent years, several eco-friendly processes for the rapid synthesis of silver nanoparticles have been reported using aqueous extracts of plant parts such as the leaf, bark, roots, etc. This review summarizes and elaborates the new findings in this research domain of the green synthesis of silver nanoparticles (AgNPs) using different plant extracts and their potential applications as antimicrobial agents covering the literature since 2015. While highlighting the recently used different plants for the synthesis of highly efficient antimicrobial green AgNPs, we aim to provide a systematic in-depth discussion on the possible influence of the phytochemicals and their concentrations in the plants extracts, extraction solvent, and extraction temperature, as well as reaction temperature, pH, reaction time, and concentration of precursor on the size, shape and stability of the produced AgNPs. Exhaustive details of the plausible mechanism of the interaction of AgNPs with the cell wall of microbes, leading to cell death, and high antimicrobial activities have also been elaborated. The shape and size-dependent antimicrobial activities of the biogenic AgNPs and the enhanced antimicrobial activities by synergetic interaction of AgNPs with known commercial antibiotic drugs have also been comprehensively detailed.

1. Introduction

Currently, modified or fabricated of NPs is widely utilized in industrially manufactured items e.g. , cosmetics, electronics, and textiles. Furthermore, the rapid increased in the number of microbes resistant to existing antibiotic drugs that has led to the requirement of novel medicines in the form of bare NPs or in conjunction with existing antibiotics to exert a favourable synergistic effect resulted in the wide spread use of NPs in several medical fields. 10,11 Nowadays, NPs have been utilized for molecular imaging to achieve profoundly resolved pictures for diagnosis. In addition, contrast agents are impregnated onto NPs for the tumour and atherosclerosis diagnosis. 12–14 Furthermore, nanotherapeutic has been promoted everywhere throughout the world after the first FDA affirmed nanotherapeutic in 1990, to build up different nano-based drugs. 15

At the beginning of 20 th century, various physical and chemical methodologies such as chemical reduction, milling etc. , have been utilized for the synthesis of NPs synthesis as well as to enhance its efficiency. 16 However, these conventional techniques involve costly and toxic chemicals and cannot be considered an environmentally benign process. 17 Taking into account, nowadays researchers showed great interest on the synthesis of metal and metal oxides NPs employing bio-genic route, that utilized aqueous plant extract and microbes, as they are environment-friendly, stable, clinically adaptable, bio-compatible and cost-effective. 16,18 Therefore, bio-inspired technology for NPs synthesis became a significant branch in the field of nanoscience and nanotechnology. 19,20 Till now, numerous metal and metal oxide NPs have been synthesized using plant extract and microbes etc. 21,22 Owing to their wide availability, renewability and environment-friendly nature, in addition to their vast applications in the synthesis of NPs, plant biomass are also largely targeted by our group and others as a catalyst for chemical synthesis 23,24 and biodiesel productions. 25,26

Among metal NPs, silver NPs is gaining enormous interest in the research community due to their wide scope of application in microbiology, chemistry, food technology, cell biology, pharmacology and parasitology. 27,28 The morphology of the silver NPs is the deciding factor of their physical and chemical properties. 28 Basically, several techniques such as sol–gel method, hydrothermal method, chemical vapour deposition, thermal decomposition, microwave-assisted combustion method etc. , have been utilized for the synthesis of silver NPs. 29–31 Recently, bio-genic synthesis of silver NPs (AgNPs) using biomaterials such as plant extract and microbes as reducing agent and their antimicrobial activity is widely investigated. 32,33 AgNPs are produced by oxidation of Ag + to Ag 0 by different biomolecules such as flavonoids, ketones, aldehydes, tannins, carboxylic acids, phenolic and the protein of the plant extracts.

UV-visible spectroscopy is a simple and widely used analytical technique to monitor the formation of AgNPs. Upon interaction with an electromagnetic field, the conducting electrons present in the outermost orbital of metal NPs collectively oscillate in resonance with certain wavelengths to exhibit a phenomenon called surface plasmon resonance (SPR). The excitation of SPR is responsible for the formation of color and absorbance in a colloidal solution of AgNPs. The SPR peaks at around 435 nm are usually taken to confirm the reduction of silver nitrate into AgNPs. 34 In general, spherical NPs exhibit only a single SPR band in the absorbance spectra, whereas two or more SPR bands were observed for anisotropic particles depending on the shape. 35 The absence of peak in the region 335 and 560 nm in UV-Vis spectra are sometime used as an indication of the absence of aggregation in NPs. 32,36

Statistical data analysis in Fig. 1 depicted the increasing trend of published research papers in the field of biogenic synthesis of AgNPs. These data were collected in September 2020 from “SciFinder Database” using the keyword “Green synthesis of silver nanoparticles”. From a meagre 259 publications in the year 2001, it has exponentially increased to 3374 publications in 2019. Thus, in this review, an attempt has been made to inspire the researchers to explore the natural resources to synthesize silver nanoparticles by diverse plants and their organs to interconnect nanotechnology with biotechnology into one, termed as nanobiotechnology. This review will also unlock ideas to utilize different paths for the production of silver nanoparticles, which can help human beings. We have comprehensively discussed the bio-genic synthesis and silver nanoparticles using various plants and their application in antimicrobial activity. We also discussed the effect of the synthesized silver nanoparticles' size and shape in antimicrobial activity towards various pathogenic bacteria. In an attempt to synthesize metals NPs one has to bear in mind that the success of NPs depends not only on the size and shape but also on stability of NPs as they have the tendency to form large aggregates that lead to precipitation, thereby reducing their efficacy.

2. Protocols for the biosynthesis of AgNPs

2.1 from plant extract, 2.2 from microbes, 3. plant-mediated biogenic synthesis of agnps and their antimicrobial activity, 3.1 from leaf.

Clitoria ternatea and Solanum nigrum 58 were also reported to synthesize very small-size AgNPs and evaluated against B. subtilis , S. aureus , S. pyogenes , E. coli , P. aeruginosa , K. aerogenes . Interestingly, among the two leaf Clitoria ternatea extract gave smaller nanoparticles, which indicated the important role of extract constituents on the size of the produced nanoparticles. In addition, AgNPs of Clitoria ternatea showed higher activity than the AgNPs of Solanum nigrum against nosocomial pathogens due to its small size. It has been well-documented in literature that smaller size NPs showed higher antimicrobial activities due to larger surface area. 56 Grewia flaviscences , 59 Prunus yedoensis , 60 Justicia adhatoda L, 61 Withania somnifera 62 produced AgNPs in the range 8–100 nm which mainly are spherical. Numerous microbes such as skin bacteria are responsible for skin infection and body odor, as well as odor in feet, shoes, and/or socks mediated through the breakdown of amino acids present in sweat. Hence proper medication is required for human's wellbeing. Velmurugan et al. 60 applied the synthesized AgNPs from Prunus yedoensis to treat P. acnes , S. epidermidis , a well-known skin bacteria, and found that the synthesized NPs are more effective against skin bacteria than commercial AgNPs. The biogenic AgNPs showed 18 mm ZOI (zone of inhibition) in 30 μg scale against P. acnes , whereas commercial AgNPs displayed a lower ZOI of only 12 in the same concentration.

Pistacia atlantica , 63 Tectona grandis Linn, 64 Ficus virens 65 also reported for the synthesis of AgNPs and are evaluated against several microbes. Verma et al. 66 reported Azadirachta indica (neem) leaf inspired synthesis of AgNPs and evaluated the effects of pH of the solution on the formation of nanoparticles as change in pH affects the shape and size of the particles by altering the charge of biomolecules, which might affect their capping as well as stabilizing abilities. They have observed that as the pH increases from 9 to 13, the absorption maximum shifts from 383 to 415 nm in the UV-spectrum and detects an increase in absorption intensity with increasing pH. This showed that pH 13 is the most favourable pH for the synthesis of AgNPs leaf extract. The shift in the peak wavelength indicates that the size of the particles increases with increasing pH of the solution. As the particles' diameter gets larger, the energy required for excitation of surface plasmon electrons decreases, as a result the absorption maximum shifted towards the longer wavelength region. Moreover, it was observed that at acidic pH i.e. pH < 7, the formation of nanoparticles is suppressed. At high pH, the bioavailability of functional groups in Azadirachta indica leaf extract promoted the synthesis of nanoparticles. However, at very high pH i.e. pH ∼13, the particles became unstable and agglomerated, when kept for overnight.

AgNPs were also recently synthesized using several leaf extract of plants such as Artocarpus altilis , 67 Crotalaria retusa , 68 Cardiospermum halicacabum , 69 Psidium guajava , 70 Cassia fistula 71 and Terminalia chebula . 72 In 2016, Anandalakshmi et al. 73 reported Pedalium murex leaf extract mediated AgNPs. The produced NPs were tested against several microbes and displayed highest ZOI of 10.5 mm (in 15 μL mL −1 scale) against E. coli and P. aeruginosa and least activity against Klebsiella pneumoniae (8.5 mm). The shape and size of the resultant AgNPs were elucidated with the help of TEM. The TEM micrographs showed that the sizes of the particles were around 50 nm and were predominantly spherical in shape. The PXRD pattern showed fcc crystal structure. Azadirachta indica promoted synthesis of AgNPs was reported by Ahmed et al. 74 The produced NPs displayed equal efficacy (9 mm ZOI) against E. coli , S. aureus whereas the plant extract show no antimicrobial activity.

Croton bonplandianum mediated AgNPs were also found to be highy active against microbes. 75 The minimum inhibitory concentrations of synthesized AgNPs were found to be 50, 45, 75 g mL −1 in case of E. coli , P. aeruginosa , and S. aureus respectively. It was concluded that Gram-negative strains of bacteria with thin cell wall such as E. coli and P. aeruginosa are more susceptible to cell wall damage compared to Gram-positive strain bacteria with a thick cell wall ( S. aureus ). In another work, Tamarix gallica leaf extract was used for synthesis of AgNPs. To test its activity against E. coli , three sterile filter paper discs (5 mm diameter) were impregnated with 6 μL of AgNPs produced with 5 mL of Tamarix gallica extract and 10 mL of 5 mM AgNO 3 solution, López-Miranda et al. studied the green synthesis of AgNPs using and evaluated the effect of extract and AgNO 3 concentration on the synthesis. 76 They have observed an increase in the intensity of surface plasmon resonance (SPR) with the increase in extract concentration, which is attributed to an increasing number of AgNPs formed. Also, as the AgNO 3 concentration increases, many silver ions are increasingly reduced to AgNPs. However, they have seen that the SPR band intensities are nearly independent for 5, 7, and 9 mM AgNO 3 , which reflected that the reaction is close to an equilibrium system because the reducing compounds and stabilizers from the extract are completely consumed, hence it is impossible to reduce a larger amount of silver ions. Henceforth, from the UV-vis analysis they concluded that the best results were obtained for the sample 0.15 g mL −1 extract with 5 mM AgNO 3 . The produced showed 9 mm ZOI against E. coli . Similarly, leaf extract of Urtica dioica , 77 Ziziphus oenoplia 78 and Lawsonia inermis 79 are reported for the production of AgNPs with high antimicrobial activities. In 2016, a remarkable work on the synthesis of AgNPs using Urtica dioica leaf extract that showed excellent synergistic effect with known antimicrobial drugs was reported by Jyoti et al. 77 Interestingly, the synthesized AgNPs apart from showing high antimicrobial activities against several microbes, showed excellent synergistic effect in combination with antibiotics and displayed higher antibacterial effect as compared with AgNPs alone. A high 17.8 fold increase in ZOI was observed for amoxicillin with AgNPs against S. marcescens proving the synergistic role of AgNPs. 77 This work provides helpful insight into the development of new antibacterial agents to fight against several new stain of microbes resistant to existing antibiotic drugs. Fig. 4 displayed the synergistic effect of AgNPs and common antimicrobial drugs. The synergistic interaction between AgNPs and antibiotic drugs has been clearly identified using UV-Vis and Raman spectrometer by McShan et al. 80 The authors claimed that this synergistic interaction speed up the ejection of Ag + from AgNPs which inturn boost its antimicrobial activities.

Recently, Manjamadha et al. 81 have reported ultrasonic-assisted biosynthesis of spherical AgNPs using Lantana camara L. leaf extract. Biosynthesis of AgNPs using ultrasonication improves the reaction conditions such as reducing reaction time and enhancing the reaction rate. Bactericidal activity of the synthesized AgNPs revealed that it shows excellent antibacterial activity against Gram-positive and Gram-negative bacteria. Leaves of Jatropha curcas collected from Micro model complex, Indian Institute of Technology Delhi campus was used for the production of AgNPs. 82 The transmission electron microscopy (TEM) analysis showed variation in particle shape and size (20–50 nm), whereas the diameter of NPs was found to be in range of 50–100 nm by scanning electron microscopy (SEM). Complete destruction of the microbial cell was visible using TEM examination. The synthesized NPs were tested for their antimicrobial activities and based on ZOI data, the pattern of sensitivity was observed in the order as E. coli > P. aeruginosa > B. cereus > S. enterica = L. monocytogenes > S. aureus .

Salvinia molesta , 83 Sesbania grandiflora , 84 Indoneesiella echioides 85 and Phlomis 86 leaf extract were also useful for the bioreduction of AgNO 3 to AgNPs. An ultra-small AgNPs with an average diameter of 7.39 nm were prepared using Hydrocotyle rotundifolia . 87 The synthesized AgNPs were tested for its antimicrobial property against E. coli (DH5α). The MIC value was recorded as 5 μg mL −1 and demonstrated significant growth inhibition on agar plate. Formation of spherical AgNPs using Maclura pomifera was achieved in 2017 by Azizian-Shermeh et al. 88 The produced NPs (0.1 mg mL −1 concentration) displayed a very high ZOI of 23.4 ± 0.1 mm against E. coli , which is higher than Ampicillin, a well-known antibiotic drug. In the same year, Bhuyan and coworkers at National Institute of Technology Silchar reported Paederia foetida Linn. inspired AgNPs synthesis. 89 The order of activities of the AgNPs against tested microbes is B. cereus > E. coli , S. aureus > A. niger . The author claimed that the AgNPs owing to their small size range (5–25 nm) could have easily penetrated the cell membrane, disturbing the metabolism, cause irretrievable damage finally leading to the microbial cell death. Au NPs has also been synthesized but has not shown any antimicrobial activity which testament the higher activity of AgNPs than that of Au NPs. Biosynthesized AgNPs from leaf extract of Atalantia monophylla , 90 Talinum triangulare , 91 Ricinus communis , 92 Erythrina suberosa , 93 Lippia citriodora , 94 and Brassica oleracea L. 95 are also successfully used as an outstanding antimicrobial drug.

In 2017 Al-Shmgani et al. prepared AgNPs using Catharanthus roseus . 96 They have used identification by color change, UV-vis spectrum, XRD, FTIR, and AFM techniques to confirm the biosynthesis of AgNPs. The leaf extract color changes from yellowish to reddish-brown after adding 2 mM AgNO 3 and exposing to heat at 70 °C for 3 min indicating the formation of the NPs. AFM displays the crystalline NPs with grains sized 10–88 nm in diameter with mean size of about 49 nm. The authors claimed that synthesized AgNPs enter the cell of microbes that resulted in a disruption of adenosine triphosphate (ATP) production and DNA replication, generation of ROS and damage the cell structures as earlier observed by Sahayaraj and Rajesh. 97

Spherical shape AgNPs with diameter in the range 11–47 nm (by TEM analysis) were produced using Lavandula x intermedia . 98 The AgNPs were found to be most effective against E. coli among all the tested microorganisms shown in Table 1 , entry 51. Interestingly, the author also observed that biogenic AgNPs showed ZOI 23 ± 0.0 mm against E. coli whereas streptomycin displayed only 20 ± 0.0 mm under the same concentration. This reflected the high antibacterial efficacy of AgNPs than that of common antimicrobial drug like streptomycin, which could promote its wide use in the future. In another work, a highly crystalline AgNPs were reported to be synthesized from Canna edulis . 99 The NPs showed highest antimicrobial activity against S. typhimurium which is closely related to the finding by Sumitha et al. 38

In 2017 Artemisia vulgaris mediated AgNPs were reported by Rasheed et al. 100 Antimicrobial test revealed that the AgNPs exhibited significant inhibition activities against tested pathogens with the highest value being recorded against S. aureus (18 ± 0.27 mm inhibition zone). Similar to this, earlier in 2016, Thatoi et al. 101 reported high activity of AgNPs against S. aureus using AgNPs synthesized from Sonneratia apetala plant extract.

Psidium guajava was applied for the production of spherical AgNPs with average dimension of 25 nm. 102 The authors observed that for 100 μg mL −1 Psidium guajava mediated AgNPs, the ZOI were 18.13 ± 0.02 mm and 16.92 ± 0.18 mm against A. faecalis and E. coli , respectively, whereas ZOI of 13.24–14.41 mm were recorded at the same concentration against tested Gram-positive bacteria shown in Table 1 , entry 54. This finding clearly testament the higher activity of the synthesized AgNPs towards Gram-negative bacteria than the Gram-positive ones. Similar to this finding, earlier in 2013, Geethalakshmi et al. also reported the higher susceptibility of Gram-negative bacteria to silver nanoparticles compared with Gram-positive bacteria. 103 Ironically, Psidium guajava mediated AgNPs is however consistently less sensitive towards tested fungi such as S. cerevisiae , A. niger and R. oryzae as compared to both Gram-positive and Gram-negative bacteria.

Taraxacum officinale leaf extract mediated AgNPs were proved to exhibit an excellent synergistic antibacterial activity with standard antibiotics (such as oxy-tetracycline, tetracycline, ampicillin, and streptomycin) and showed strong positive response against both X. axonopodis , P. syringae , a plant pathogens. 104 The combined effect of tetracycline with AgNPs significantly inhibited the growth of selected phytopathogens by increasing ZOI about 40% compared to only antibiotics. The authors are of the opinion that NPs-antibiotic combination and their synergistic action would result in higher penetration in the bacterial cell membrane thereby leads to destruction of various cell organelles and death of bacteria, although the mechanism is not yet fully understood till now.

Lateef et al. 105 reported that Petiveria alliacea L. mediated AgNPs showed 100% inhibition against E. coli , K. pneumoniae , S. aureus , A. fumigatus and A. flavus . But only 66.67% inhibition in A. niger . In another work, microwave-assisted synthesis of AgNPs using leaf extract of Nervalia zeylanica was reported. 106 The authors observed no formation of NPs (monitored using UV-spectroscopy) even after 5 h under RT stirring of the extract and AgNO 3 . However, the nanoparticle formation takes place suddenly after 60 s of microwave irradiation. Ficus ingens mediated AgNPs recorded MIC value of 10 μg mL −1 on E. coli and 20 μg mL −1 on both S. typhi and B. cereus 107 which is in close agreement with the earlier report of 10 μg mL −1 for E. coli . The AgNPs showed highest inhibition against E. coli and least with S. cereus . Commercial antibiotic Ciprofloxacin showed better activities than the synthesized NPs.

In general, the reduction in the size of the metallic nanoparticles is expected to increase the antibacterial activity due to significantly large surface area of the smaller nanoparticles. However, the results obtained by Erci et al. 108 using Thymbra spicata leaf extract is worth discussing. In their study higher antibacterial activity of, say, AgNPs2 (average diameter 70.2 nm) in comparison to AgNPs1 (average diameter 25.1 nm) was recorded. They reasoned that this could be due to the shape of AgNPs2, which have triangles, hexagons, spheres and irregular shapes, whereas AgNPs1 exhibit mostly spherical formation. This interesting finding confirmed the shape-dependent bacterial activity of AgNPs, and support earlier reported protocol. 109 The MIC of 50 μg mL −1 was recorded for S. cereus whereas, it was 100 μg mL −1 for E. coli . This finding is in sharp contrast to the work of Kavaz et al. 107 mentioned earlier where Gram-negative bacteria has lower MIC than Gram-positive bacteria. However, Erci et al. 108 defended their finding of the more pronounced effect of AgNPs against Gram-positive bacteria than Gram-negative bacteria based on the structural difference in cell wall composition of Gram-positive and Gram-negative bacteria. Gram-negative cell wall was covered with an outer lipid membrane (lipopolysaccharide), which is more negatively charged than Gram-positive. As is evident from the zeta value, the biogenic silver nanoparticles were also negatively charged and the electrostatic repulsion between the nanoparticles and Gram-negative bacteria hinders particle attachment and penetration into the cell 37 However, this postulate is not yet fully understood. Again, as against the finding of Erci et al. 108 the Gram-positive bacteria are less affected by AgNPs (produced from Indigofera tinctoria ) than Gram-negative bacteria as reported by Vijayan et al. 110 The authors credited the presence of large number of peptidoglycan layers on the walls of Gram-positive bacteria than Gram-negative bacteria that have to some extent prevent the nanoparticles entry to cytoplasmic membrane than Gram-negative bacteria. Hence, the true role of chemicals in the cell wall of bacteria needed to be properly investigated to understand the underlying mechanism of the cell death due to NPs.

Another interesting work on the shape-dependent activity of biogenic AgNPs was reported using Trichoderma viride extract where the authors reported a higher antimicrobial activity of penta- and hexagonal NPs than spherical NPs when the size are of similar range. 111 The different shape AgNPs such as pentagonal, hexagonal and spherical were synthesized by manipulating physical parameters, temperature, pH, and reaction time. At neutral pH (7), spherical NPs were observed under all reaction conditions. Delightfully, at pH 5.0 and 9.0, rectangular and penta-/hexagonal NPs were obtained at 40 °C after 72 h of incubation. In general, longer is the reaction, bigger is the size of NPs whereas higher temperature always affords a smaller NP. It was also found that triangular shape AgNPs showed better antimicrobial activity compared to that of spherical and rod shaped as it has high percentage of facet (1 1 1) that possess a high atomic density which increases binding efficiency of Ag to sulfur containing components, whereas spherical and rod shaped particles have a high percentage of (1 0 0) facets. 112,113

Recently, Tecoma stans , 114 Salvia leriifolia , 115 Leucaena leucocephala L. 116 and Selaginella bryopteris 117 were also reported to produced AgNPs which are mainly spherical in nature. Galega officinalis leaf extract mediated AgNPs with size-dependent activities were reported by Manosalva et al. 118 AgNPs with 23 nm and 220 nm recorded MIC of 5 μL mL −1 and 30 μL mL −1 respectively against E. coli showing the higher activity of the smaller NPs. Interestingly MIC of S. aureus (a Gram-positive bacteria) is higher (50 μL mL −1 ) than E. coli (a Gram-negative bacteria) using 23 nm size AgNPs which implies the higher activity of AgNPs against Gram-negative bacteria.

In the year 2019, antimicrobial fabric tests on the dyed cloths were conducted using AgNPs derived from Camellia sinensis (tea leaf) extract where bleached cotton cloths were dyed using the NPs colloidal solutions. The attachment of AgNPs on the cloths was confirmed by SEM. SEM images of AgNPs with green tea extract also showed the generation of AgNPs. The AgNPs showed excellent antimicrobial activities against S. aureus , K. pneumoniae in the cotton fabric which potentially endorse the suitability of using AgNPs as an effective antimicrobial in cloths. 119 Bernardo-Mazariegos et al. used DLS to measure the average hydrodynamic size and zeta potential of the AgNPs synthesized from Justicia spicigera . 120 The sample with a mixture of AgNPs of different sizes gave two broad peaks and was weighted toward the larger particles ( z -average size of 4.04 μm and 192 nm). The authors are of the opinion that DLS measurement may not be accurate for polydisperse samples due to its nature to respond toward larger particles. Additionally, the zeta potential was of the NPs was found to be 0.2 mV that indicated the less stability and hence, a tendency to agglomerate to form large particles.

In recent times, highly antimicrobial AgNPs were synthesized using Kleinia grandiflora , 121 Eucalyptus citriodora , 122 Juniperus procera 123 and Capparis zeylanica . 124 Two different shapes structure in the form of sphere and cubic are observed in SEM analysis of the AgNPs generated from Juniperus procera leaf extract. The produced NPs recorded the highest ZOI against P. mirabilis measured at 29 ± 1.3 mm. The author suggested that the high antimicrobial activity of the NPs is due to the inherent activity of the NPs coupled with the plant particulates attached to the NPs, as the plant which contain high flavonoids and polyphenols are a well-known antimicrobial by themselves. 125 Small size AgNPs (9 nm) synthesized using Caesalpinia pulcherrima leaf extract were found to exhibited an MIC as low as 0.078 mg mL −1 and 0.156 mg mL −1 for K. pneumoniae and E. coli respectively. Accordingly, the AgNPs possessed maximum antimicrobial activity against K. pneumoniae and E. coli whereas only moderate effects were shown against C. xerosis , S. mutans , S. aureus , S. viridians , S. pyrogenes , S. viridians and C. diphtheriae that have higher MICs. 126

Aesculus hippocastanum (horse chestnut) mediated special AgNPs with size 50 ± 5 nm was reported to have highest antimicrobial activity (ZOI 20.0 ± 0.00 mm) against a Gram-negative bacteria P. aeruginosa among all the tested microorganisms listed in Table 1 , entry 74. 128 Interestingly, although the AgNPs have profound effects on all the tested bacteria, it have no effect against fungal strains such as C. albicans ATCC 10231, C. tropicalis ATCC 13803 and C. krusei ATCC 1424. The MIC and MBC of AgNPs for the tested microorganisms were in the range from 0.19–12.5 μg mL −1 and 1.56–25 μg mL −1 .

Ramadan et al. 129 studied the antiviral activity of green synthesized AgNPs and found that AgNPs greatly enhanced the antiviral activity of M. alternifolia leaf extract, which on its own has no effect on the tested viruses such as herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2). In addition, the NPs showed excellent activities against several persistent skin bacteria including S. epidermis and methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, tea tree oil of M. alternifolia itself showed even higher activity than the AgNPs against some tested microbes which is hardly the case in literature. In another work, Carya illinoinensis mediated AgNPs were found to be more efficient against Gram-negative ( E. coli ) than Gram-positive bacteria ( S. aureus ) 130 in a similar trend reported earlier. 118

Although literature revealed that bacterial cell are generally more sensitive to AgNPs, biogenic AgNPs derived from Murraya koenigii leaf extract interestingly shown highly equal activity against Gram-negative bacteria P. aeruginosa (ZOI of 18 mm) and a fungus C. albicans (18 mm ZOI). 131 In 2020, several leaf extracts of plant such as Clerodendrum inerme , 132 Aspilia pluriseta , 133 Melia azedarach , 134 Scoparia dulcis , 135 and Lantana trifolia . 136 All these AgNPs are shown to exhibit an excellent antimicrobial activity against numerous common pathogenic microbes. Mikania micrantha leaf extract mediated AgNPs were also reported to show a high ZOI of 26.17 mm and 26.05 mm against B. subtilis and E. coli respectively. 137

More recently, AgNPs of average size 3.46 nm were produced using Solanum nigrum plant leaf extract. 138 This is one of the smallest biogenic AgNPs reported so far and NPs as small as 1.74 nm were observed. SPR bands band at 442 nm in UV-visible spectroscopy confirmed the formation of AgNPs. Interestingly, the authors observed a much prominent antimicrobial activity exerted by AgNPs compared to AuNPs and PdNPs potentially due to the more effective capping of AgNPs nanoparticles than either Au or PdNPs which results in well-dispersed small AgNPs without much agglomeration as detected by HRTEM. The authors are of the opinion that polyphenols present in Solanum nigrum extract forms a negative environment around the particles and hence create a repulsive force which overcomes the van der Waals force of attraction and prevent AgNPs agglomeration. The AgNPs showed 22 mm ZOI, while 20 mm and 19 mm ZOI are observed in Au and Pd NPs respectively against E. coli at 10 μL mL −1 concentration. However, although the authors credit the effective capping of AgNPs as a reason for its higher antimicrobial activity, it may also be due to the smaller size of the AgNPs (3.46 nm) as compared to Au (9.39 nm) and Pd NPs (21.55 nm).

Maghimaa et al. 139 reported biosynthesis of AgNPs using Curcuma longa leaf extract and investigate their antimicrobial activity in AgNP coated cotton fabric. The loading of AgNPs on the cotton fabric was confirmed by SEM analysis, which was further assisted by the EDX analysis. The authors have reported that the cotton fabric loaded with AgNPs showed great resistance to the growth of pathogenic microorganisms and hence they claimed that the cotton fabric loaded with AgNPs synthesized from Curcuma longa can be used for the diverse application in the medical patient as well as in medical workers to resist microbial infection.

In 2020, green synthesis of spherical AgNPs, CuNPs and FeNPs with size 11–19, 28–35 and 40–52 nm, respectively using Syzygium cumini leaf extract was reported. 140 The order of antibacterial property against methicillin- and vancomycin-resistance S. aureus , A. flavus and A. parasiticus microbes was found to be Ag- > Cu- > Fe NPs, which linearly relates with the size of the NPs, thereby reinforcing the size-dependent activity of NPs. 141 In addition, the bioproduction of aflatoxins (a family of toxins produced by certain fungi that are found on agricultural crops such as maize (corn), peanuts, cottonseed, and tree nuts) in A. flavus and A. parasiticus was also significantly inhibited by AgNPs when compared with the Fe and Cu NPs. Interestingly, the pH of the plants extract reduced after the formation of NPs in all the cases. Cleistanthus collinus 142 and Cestrum nocturnum 143 are also known to have produced AgNPs.

In another work, rice leaf extract was utilized for the biosynthesis of AgNPs with size 16.5 nm. 144 Antifungal activity of the synthesized NPs was tested against mycelium and sclerotia of R. solani , a fungus that causes sheath blight disease in rice and found that it inhibits the growth of fungus and the growth inhibition is dependent on the concentration of the AgNPs. The MIC values of AgNPs were in the range of 5–10 and 15–20 μg mL −1 towards fungal mycelium and sclerotia, respectively. Results revealed that growth inhibition at 10 μg mL −1 AgNPs is 81.7–96.7% for mycelium and 20 μg mL −1 treatment completely inhibited disease cause by R. solani . In a previous investigation, 43.3–73.6% growth inhibition of R. solani was observed at a higher concentration of 2 mg mL −1 with larger AgNPs with 40–60 nm. 145

Recently, an ultra sound-assisted AgNPs of size 8 mm were synthesized using Mentha aquatica leaf extract as reducing and capping agent. 146 To the best of our knowledge, this is the smallest biogenic AgNPs reported so far. The production of NPs could occur at RT, but ultrasound greatly reduced the reaction time to 10 min whereas RT took 1 h. The authors highlighted that the phenolic compounds in the Mentha aquatica leaf extract get oxidized to Quinone in an alkaline condition which provides free electrons for reduction of the Ag + ion to Ag 0 to form the desired AgNPs. Largely due to its ultra-small size, the AgNPs displayed a very low MIC of 2.2 μg mL −1 for P. aeruginosa , which showed its high efficacy against the tested microbe.

Rosemary ( Rosmarinus officinalis Linn.) 147 and Ceropegia thwaitesii 148 leaf extract mediated AgNPs which showed consistent higher activities against Gram-negative bacteria were also reported. Interestingly, S. flexneri , S. typhi , B. subtilis , M. luteus , and P. mirabilis are more susceptible to AgNPs than E. coli 148 which is not very common in literature.

In the year 2015, Gavade et al. prepared AgNPs using the leaf extract of Ziziphus jujuba under RT. 149 The AgNPs have different shapes with 20–30 nm size as revealed by TEM images. The authors investigated the effect of pH on the size and stability of the NPs, and observed form UV-Visible spectroscopic graphs that absorbance value linearly increases with increasing pH increases from 4 to 9, which indicates the rate of formation of AgNPs increases from acidic to basic medium. In addition, at acidic pH, bands were wider and display red shift which is an indication of increase in particle size. However, in basic condition, bands were narrow and display blue shift due to decrease in particle size. The rapid formation of AgNPs in neutral and basic pH this may be due to the ionization of the phenolic groups present in the leaf extract. 150 The slow rate of formation and aggregation of AgNPs in acidic pH could be related to electrostatic repulsion of anions present in the solution. 151,152 Ironically, at basic pH there is a possibility of AgOH precipitation which need to be avoided. 150 Hence, the authors concluded that the optimum condition for the preparation of AgNPs with desired size and stability was neutral medium. The NPs have a zeta potential of −26.4 mV which is an indication of its excellent stability in colloidal state as a zeta potential higher than 30 mV or lesser than −30 mV is indicative of a stable system. 153 The AgNPs showed high efficacy against E. coli and found to be stable for more than 6 months probably due an excellent capping of NPs (indicated by FR-IR) and low zeta potential.

Irregular shape AgNPs of average size 28 nm, 26.5 nm, 65 nm, 22.3 nm and 28.4 nm were prepared from O. tenuiflorum , S. cumini , C. sinensis , S. trilobatum and C. asiatica , respectively. 154 Among several tested microbes the highest antimicrobial activity of AgNPs synthesized by S. trilobatum and O. tenuiflorum extracts was found against Gram-positive bacteria S. aureus (30 mm ZOI) and Gram-negative bacteria E. coli (30 mm) respectively. Interestingly, C. sinensis , S. trilobatum and C. asiatica derived AgNPs consistently showed higher susceptibility towards a Gram-positive bacteria S. aureus and Gram-negative bacteria E. coli and K. pneumoniae . These findings clearly shown that some AgNPs are more sensitive towards a Gram-positive bacteria whereas some towards a Gram-negative bacteria, hence the question of selective sensitivity of biogenic AgNPs toward Gram-positive or negative bacteria still remains unsolved. Is the selectivity depending on the biomaterial capping agents attached to NPs or the size of NPs? Hence, one may need to consider the biomolecules present in the plant extract or the size of AgNPs to truly understand the selectivity.

A globular shape AgNPs were prepared using Amaranthus gangeticus Linn leaf extract in 2015 which exhibited an inhibitory activity towards Gram-positive, Gram-negative bacteria as well as fungus. 155 In another work Andrographis paniculata leaf extract produced a rarely reported cubic shape AgNPs. 156 Study on different shape of AgNPs is of great interest due to the shape-dependent activities of AgNPs towards microbes as noted earlier. 109 The AgNPs showed a high ZOI of 21.3 ± 0.4 mm for Gram-negative bacteria P. aeruginosa with very low MIC of 3.125 μL mL −1 which testament its high antimicrobial activity. Yao et al. 157 noted that the thickness of the peptidoglycan layer of other Gram-negative bacteria such as E. coli is somewhat more than P. aeruginosa , hence the author, in good agreement with Yao's work, observed a lower ZOI (16.6 ± 0.3 mm) in case of E. coli .

Elangovan et al. 158 reported the biosynthesis of AgNPs having cubic, pentagonal and hexagonal shape with size range of 68.06–91.28 nm using Andrographis echioides leaf extract and investigate its bactericidal activity against several microbes. The result revealed a high ZOI in the case of E. coli (28 mm) and S. aureus (23 mm) in 100 μg mL −1 concentration of AgNPs. Azadirachta indica (neem) leaf extract was also reported for the green synthesis of polydisperse AgNPs at RT and evaluated as a potent antimicrobial agent against P. nitroreducens , a biofilm-forming bacterium and fungus A. unguis . 159

While most biogenic AgNPs are spherical, a flower-like structure was reported by Ajitha et al. in 2017. 160 The AgNPs showed very high activity towards bacterial culture Pseudomonas spp. (ZOI of 11 mm) even at very low AgNPs concentration (8 μL mL −1 ). It is worth note that the AgNPs also consistently displayed a better activity in fungal strain, Penicillium spp. than bacteria such as E. coli and Staphylococcus spp. which is hardly a case in any literature as bacteria are usually considered more sensitive to AgNPs than fungi.

3.2 From seeds

Pimpinella anisum , 163 Synsepalum dulcificum , 164 Vigna radiate , 165 Dracocephalum moldavica 166 leaf extracts were also successfully applied for the green synthesis of AgNPs. Vigna radiata mediated AgNPs, was found to be more susceptible towards Gram-negative bacteria E. coli (ZOI 20 mm) than Gram-positive S. aureus (ZOI 16 mm) due to the higher thickness of the peptidoglycan layer (approx. 80 nm thick) of the cell wall of Gram positive bacteria which is 10 times thicker than the peptidoglycan Gram-negative bacteria, hence is less susceptible to be destroyed by AgNPs. 165

Several reported literatures revealed that the efficiency of AgNPs as antimicrobial agent is extensively dependent on the shape of the nanoparticles. The comparison of spherical, disc like and triangular shaped AgNPs as antimicrobial agent revealed the activity trend follows as spherical AgNPs > disc-like AgNPs > triangular AgNPs. 65,136 The highest inhibition effect of 94.1% and 84% were observed at 40 ppm concentration of AgNPs against R. solani and N. parvum respectively, using AgNPs derived from Trifolium resupinatum seeds extract. 167 In a closely related study, Khatami et al. reported more than 86% inhibition of mycelium growth of R. solani at a concentration 25 μg mL −1 (or 25 ppm) of the biogenic AgNPs. 168 Several plant seeds such as Nigella arvensis , 169 Linseed , 170 Embelia ribes , 171 Melissa officinalis 172 are applied for the generation of spherical shape AgNPs. While biogenic AgNPs are reported to be more efficient antimicrobial than any other metal NPs in most of the case, it is worth mentioned that the Embelia ribes derived AgNPs is less susceptible to E. coli at showing ZOI of 20 mm against 28 mm ZOI for AuNPs at 250 μL mL −1 concentration. 171 Although having small size of NPs (6–25 nm), Leucaena leucocephala mediated AgNPs displayed very low toxicity against both E. coli and S. aureus with ZOI of 18 mm and 22 mm (approx.) respectively at 1000 ppm AgNPs concentration. 173 Alpinia katsumadai seeds extract mediated AgNPs showed excellent activities against E. coli and S. aureus than that of P. aeruginosa , 174 whereas those derived from Myristica fragrans are found to be highly sensitive to multidrug-resistant (MDR) Salmonella enterica serovar typhi ( S. typhi ) where a highest ZOI of 16.4 ± 0.45 was observed at 100 μg μL −1 concentration of AgNPs. 175

Common skin bacteria such as P. acnes and S. epidermidis are found to be highly inhibited by AgNPs synthesized using Phoenix sylvestris L. The authors also proved that AgNPs is more susceptible to the tested shin bacteria than the seeds extract as well as AgNO 3 solution as can be seen from the ZOI. 176 The high toxicity of Phoenix dactylifera derived AgNPs against Methicillin-resistant S. aureus is clearly seen in SEM images ( Fig. 5a–d ) and HRTEM images ( Fig. 5e and f ). Cells treated with AgNPs undergo deformities and irregular cell surface (red arrow). Attachment and penetration of NPs and deformities of the outer most layers of cell wall and cytoplasmic membrane are also clearly visible in HRTEM. 177

The seeds extracts of plants such as Tectona grandis , 178 Persea americana , 179 Salvia hispanica L 180 and Trigonella foenum-graecum 181 produced AgNPs with high antimicrobial activities. Interestingly the size of AgNPs depends on the concentration of Persea americana extract where a small NPs was recorded at low concentration of aqueous extract, whereas high concentration results in the formation of larger NPs. 179 Ironically, the AgNPs from Salvia hispanica L showed lower susceptibility towards antibiotic Ampicillin against E. coli and S. aureus although its high ZOI against E. coli (18.5 mm) and S. aureus (14.9 mm) at 7.7 μL mL −1 concentration. 180

The increase in lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) enzyme concentration were used as a means to visualize the change in physiology and inhibition caused to microbes such as S. aureus (263 U L −1 ) and S. aureus (263 U L −1 ) by Trigonella foenum-graecum mediated AgNPs. 181 This increase in enzyme reflected that bacteria are under stress conditions due to unfavorable environment on treatment with AgNPs. 182 Synergistic behavior of ampicillin with Hibiscus cannabinus seeds produced AgNPs against S. aureus , B. cereus , E. coli was investigated by Adnan et al. in 2020. 183 Biogenic AgNPs that possessed high inhibitory effect on biofilms formation in P. aeruginosa , C. violaceum and S. marcescens was reported. 184 The biofilms of P. aeruginosa was inhibited by 10.6, 18.8, 36.1, 62.0, and 77.6% in presence of 1, 2, 5, 10, and 15 μg mL −1 of Carum copticum mediated AgNPs respectively.

In their effort to synthesize AgNPs from Pimpinella anisum seeds extract, Zayed et al. systematically studied to influence of different parameters such as extraction solvent used, extraction temperature, solvent/plant ratio and extraction time which are crucial for the successful synthesis of AgNPs. 185 Hexane, methylene chloride, 70% methanol and water were evaluated as an extraction solvent and 70% methanol was chosen as a best solvent for the fast synthesis of NPs indicated by color change of the reaction solution, whereas this color change is very slow or not visible in other solvent extracts. The high reactivity of 70% aqueous methanol extract towards the reduction of Ag + to Ag 0 NPs is due to an excellent solubility of polyphenols in the plant seeds which is efficiently washed down during the extraction process. The SPR peak intensities of both AgNPs and AuNPs increased as the extraction temperature is raised from 25 to 60 °C. This may be due to increasing the solvent's diffusion rate into plant tissues by destroying the cell structures with raising the temperature. 31 They also observed increasing SPR by increasing the extraction temperature 25–60 °C but extraction at 60 to 85 °C resulted in decreasing SPR probably due to decomposition of bioreductant at high temperature. The solvent/plant ratio of 10 mL g −1 was optimized for the AgNPs synthesis. Increasing the ratio from 3–10 mL g −1 inceased the SPR due to increasing solubility of biomolecule, however above 10, SPR went down due to high dilution of the extract. The band intensity reached its maximum value with extracts prepared at 60 min, further increase in contact time caused a decrease in the band intensity. It was observed that as extraction time increases the mass transfer coefficient between the solute and solvent increases that potentially increase the amount of the extracted biomolecule from plants which enhance the formation of the NPs. 186 However, prolonged extraction time resulted in the thermal decomposition and oxidation of reactive biomolecules due to prolong heating. 187

Similarly, the dried and roasted coffee ( Coffea arabica ) seed was employed as a reducing and stabilizing agent for the biosynthesis of AgNPs. TEM micrographs of synthesized AgNPs ( Fig. 6 ) were revealed that the nanoparticles are spherical and ellipsoidal in structure with size ranging from (a) 10–40 nm for 0.1 M, (b) 10–50 nm for 0.05 M and (c) 20–150 nm for 0.02 M. The biomolecules that act as a capping agent around the NPs are visible in TEM images. The SAED patterns indicated that the nanoparticles are crystalline in nature with a certain d-spacing corresponds to fcc structure. The authors investigated its bactericidal activity against E. coli and S. aureus . The results revealed that AgNPs solution of 0.05 M and 0.1 M showed a high ZOI in both cases. However, ZOI is higher against E. coli . 41

3.3 From flowers

3.4 from roots.

Ezealisiji et al. have reported the green synthesis of AgNPs using root bark extract of Annona muricata Linn and investigate their application as an antimicrobial agent against pathogenic bacteria such as B. subtilis , S. aureus , and K. pneumonia , E. coli , and Pseudomonas aeruginosa . The zone of inhibition (ZOI) in diameters were 10.00, 15.00 mm and 12.50, 17.50, 20.00 mm for the five pathogens respectively at AgNPs concentration of 5 μg mL −1 . The ZOI is increased to 12.50, 14.50 mm and 14.00, 18.50, and 26.00 mm respectively at AgNPs dose of 10 μg mL −1 . Taking into account, the authors have reported that the bactericidal activity of AgNPs is concentration-dependent. 201

Cibotium barometz , 202 Diospyros assimilis , 203 Pelargonium endlicherianum Fenzl. 204 roots derived AgNPs were also highly sensitive towards tested microorganisms. Diospyros assimilis derived AgNPs showed high ZOI (18 mm approx. at 100 μL mL −1 AgNPs concentration) against E. coli and S. aureus ; however, they showed lower activity than antibiotic chloramphenicol. 203

Interestingly the AgNPs derived from Pelargonium endlicherianum Fenzl. seed extract (using 11% ethanol extract contain gallic acid and apocynin as major phytochemicals) are monodisperse, whereas those prepared from 70% methanol extract containing gallic acid, apocynin, and quercetin as major components afforded polydisperse NPs as shown in Fig. 7 . These indicated the effect of extract solvent on the composition of the extract and nature of the synthesized AgNPs, which have further bearing on the antimicrobial activities of the NPs. 204

Protein leakage and SEM studies were used as means to study the bactericidal activities of the AgNPs using Rheum palmatum seeds extract. 205 SEM images showed abnormality in the cell wall of the tested bacteria, whereas protein was found to leak in high amount due to disruption of membrane in the bacteria when treated with AgNPs which showed the damage caused by AgNPs, which is supported by previous literature. 206 The AgNPs showed higher susceptibility towards P. aeruginosa (14.35 ± 0.24 mm ZOI) than S. aureus (10.12 ± 1.81 mm). The antimicrobial activities of AgNPs from seeds extract of Lepidium draba , 207 Angelica pubescens Maxim, 208 and Phoenix dactylifera 209 were also proven. Interestingly, Angelica pubescens mediated AgNPs showed excellent activities whereas AuNPs and root extract do not possess antimicrobial activity against the tested Gram-negative and Gram-positive bacterial strain. 208 Green synthesized AgNPs and AuNPs using Arctium lappa as potent antimicrobial agents are of great interest considering the shape and size of the NPs produced. While AgNPs are mainly spherical with average size 21.3 nm, AuNPS are with different shapes such as spherical, hexagonal and triangular geometry with average size of 24.7 nm were seen in TEM. The authors believed these differences in shape and size of AgNPs and AuNPs are due to the difference in reduction potential as well as the capping agents specific to each NPs. 210 In another work, the ZOI of Asparagus racemosus mediated AgNPs were 17.0 ± 0.89 and 16.0 ± 0 for S. aureus , B. subtilis respectively. However, the AgNPs showed low ZOI (12.33 ± 0.51 mm) E. coli . 211

Lysiloma acapulcensis extract was utilized for the green synthesis of AgNPs with size ranging from 3.2–6.0 nm. 212 It is reported that Lysiloma acapulcensis plant is widely used as a traditional medicine in Mexico for the treatment of microbial contamination. Thus, the authors reported that Lysiloma acapulcensis root extract mediated AgNPs have higher antimicrobial activity. Antimicrobial activity was tested against the different microorganisms such as E. coli , P. aeruginosa , S. aureus , C. albicans and found that the inhibition potency is in the order E. coli ≥ S. aureus ≥ P. aeruginosa > C. albicans.

Irregular, triangular nanoplates with nanorods, and spherical with average size 6–20 nm, 50–450 nm, 5–30 nm respectively recorded for seed extract, starch, and CTAB-capped AgNPs from Raphanus sativus , which reflected the crucial influence of capping agents on the size and shape of final NPs. In this study, the average NPs size were measured by dynamic light scattering (DLS) technique. The magnitude of the change in the hydrodynamic radius of CTAB-capped AgNPs lower than both extract and starch-capped ones in DLS measurement; hence, the authors proved CTAB is the best shape-directing agent. 213

3.5 From fruit

Besides, antimicrobial activity of various fruit extract such as Abelmoschus esculentus , 244 Phyllanthus emblica , 245 Aegle marmelos , 246 Nauclea latifolia , 247 Myristica fragrans , 248 Capsicum frutescens 249 and Areca catechu 250 mediated AgNPs was also tested and found that the synthesized AgNPs displayed great cell disruption of bacterial strains. The effect of solvent extract of Aegle marmelos on antimicrobial activity was tested by making fruit extract in various solvents such as petroleum, ether, methanol, acetone and chloroform and found that methanol extract of Aegle marmelos displayed highest cell disruption against B. cereus and lowest for E. coli . 246

3.6 From gum

3.7 from stem, 3.8 from bark.

Recently, Butea monosperma , 277 Syzygium cumini 278 and Diospyros montana 279 bark extract were utilized for the green synthesis of AgNPs and investigate its antimicrobial activity. The resultant AgNPs are displayed prominent cell damage to the various bacterial strains. Syzygium cumini mediated AgNPs displayed greater ZOI against the Gram-negative bacteria compared to Gram-positive bacteria as the cell wall of Gram-negative bacteria is more susceptible for the synthesized AgNPs. The study also revealed that the bactericidal activity of Syzygium cumini mediated AgNPs is more compared to the Syzygium cumini extract and AgNO 3 solution, which can attributed to the small size of the AgNPs. 278 To increase the rate of the biosynthesis process for AgNPs, the microwave technique was used by Tormena et al. 280 where they have used Handroanthus impetiginosus bark extract as a reducing as well as capping agent. Bactericidal activity of the synthesized NPs was tested against two pathogenic bacteria such as S. aureus and E. coli and found good inhibition potential to both bacterial strains with MIC value 3.1 × 10 2 μg mL −1 and 6.7 × 10 4 μg mL −1 respectively. However, the pure extract displayed a low MIC value of 2.7 × 10 3 μg mL −1 and 1.2 × 10 3 μg mL −1 for S. aureus and E. coli , respectively. Interestingly, the bactericidal activity of AgNPs is higher for S. aureus compared to E. coli ( Fig. 8 ). This is contrary to the generally accepted assumption that AgNPs are more susceptible to Gram-negative bacteria due to their thin cell-wall. However, the authors defended their claim by considering the synergetic effects of biomolecules capping agents and AgNPs.

3.9 From rhizome

3.10 from peels, 3.11 from tube/bulb, 3.12 from the whole plant, 3.13 from petals, latex, pod and callus.

Latex extract of Euphorbia antiquorum L. was employed for the green synthesis of AgNPs with size ranging from 10–50 nm. Antimicrobial activity of the synthesized AgNPs was tested against various human pathogens such as E. coli , K. pneumoniae , P. mirabilis , V. cholera and E. faecalis and showed mild inhibition activity against all mentioned pathogens. 315 Similarly, antimicrobial activity of spherical AgNPs derived from Calotropis gigantea L. against various human pathogens has been investigated and displayed remarkable activity against both Gram-positive and Gram-negative bacteria. 316 Pod extract of Cocoa was utilized for the biosynthesis of AgNPs. The synthesized nanoparticles showed great inhibition against E. coli and K. pneumonia . Moreover, the nanoparticle improves the activity of cefuroxime and ampicillin synergistically. 317 In addition, Lateef et al. 318 have reported the green synthesis of AgNPs using pod extract of Cola nitida as a reducing as well as capping and stabilizing agent. Antimicrobial activity of the synthesized AgNPs revealed that at different AgNPs concentration ranging from 50–150 μg mL −1 showed great inhibition activity against K. granulomatis , P. aeruginosa , and E. coli . Besides, incorporation of 5 μg mL −1 of pod extract of Cola nitida mediated AgNPs into the paint completely inhibits the growth of bacteria such as S. aureus , E. coli , P. aeruginosa , A. niger , A. flavus and A. fumigatus and hence can be utilized in paint manufacture industries and biomedical.

Recently, callus extract of Taxus yunnanensis has been employed as a reducing and stabilizing agent for the green synthesis of AgNPs and examined their bactericidal activity against both Gram-positive and Gram-negative bacteria. The bactericidal activity test of the synthesized AgNPs revealed that the inhibition effect is more pronounced in case of Gram-positive compared to Gram-negative bacteria. Therefore, callus extract of Taxus yunnanensis mediated AgNPs can be used in antibiotic therapeutics, an alternative to the antibacterial drug. 319 Spherical and well-dispersed AgNPs were also prepared from callus extract of Chlorophytum borivilianum L. It is reported that the synthesized nanoparticle can effectively inhibit almost all kinds of human pathogens. 320

4. Mechanism of antibacterial inhibition by bioinspired AgNPs

The possible mechanism for the antibiotic activity of AgNPs is displayed in Fig. 9 . It is reported that the smaller the size of AgNPs greater is the bactericidal activity as it provides a greater surface to the bacterial membrane. The interaction between the positively charged Ag ion with the negatively charged cell membranes led to the disruption of the cell morphology and hence cell leakage occurred, resulting in cell death. Besides, AgNPs bind strongly with phosphorus and sulfur of the extracellular and intracellular membrane proteins, thus affects the cell replication, respiration and finally, the lifetime of the cell. Apart from that, AgNPs can also bind with the thiol and amino groups of membrane protein and led to the formation of reactive oxygen species (ROS), which inhibits the cell respiration. The excellent bactericidal activity of AgNPs can be attributed to the interaction with the plasma membrane and peptidoglycan cell wall of the bacterial strain. 331 It has also been suggested that the interaction of AgNPs with cell wall increases the membrane permeability by forming pores or pits and thereby causing the death of bacteria. 332,333

5. Conclusion and future outlook

Several authors revealed that Gram-positive bacteria ( e.g. S. aureus ), due to their thick cell wall of peptidoglycan layer (∼20–80 nm thick), are less susceptible to AgNPs than Gram-negative bacteria ( e.g. E. coli ) with cell wall consisting of lipopolysaccharides at the exterior, followed underneath by layer of peptidoglycan (∼7–8 nm). 75,102,103,107,108,118,130,166,236 However, this is not the case everywhere. 108,154,194,228,230,280 In the light of this, one must look into the role of lipopolysaccharides in Gram-negative that might have acted as a shield against some AgNPs and also the synergetic effect of AgNPs and biomolecules that act as a capping that might have alter the mode of interaction of NPs with the cell wall. Hence understanding the underlying mechanism of the interaction is still a challenge.

The antimicrobial efficacy of AgNPs can be greatly enhance by its synergistic interaction with many well-known antibiotic drugs. 10,11,77,80,104,127,183,261,288,317 This opens a new and exciting opportunity in combating numerous newly evolved highly infectious multi drug-resistant microbes. Hence, this research field has become a ‘hot’ topic in recent years although it is in its infancy. To have a better insight, understanding the mechanism of interaction of the AgNPs with drugs and the alteration in the mode of attack due to the synergetic interaction towards the microbes needs to be well understood and validated experimentally.

The successful green synthesis of AgNPs and evaluation, understanding the antimicrobial activities is a complex process till today although this research field has been explored several decades. However, looking at the literature we can draw several assumptions which potentially provide us AgNPs with high antimicrobial activities. Hence, knowing the complexity of the research on the green synthesis and antimicrobial activity of AgNPs, the below points are worth considered during AgNPs synthesis:

(1) Chemical composition of the plant extract

(2) concentration of the plant extract, (3) concentration of agno 3, (4) extraction solvent, (5) extraction time and temperature, (7) reaction time, (8) reaction temperature, conflicts of interest.

• M. Ayelén Vélez, M. Cristina Perotti, L. Santiago, A. María Gennaro and E. Hynes, Bioactive compounds delivery using nanotechnology: design and applications in dairy food , Elsevier Inc., 2017  Search PubMed .
• A. Bera and H. Belhaj, J. Nat. Gas Sci. Eng. , 2016, 34 , 1284–1309  CrossRef   CAS .
• L. J. Frewer, N. Gupta, S. George, A. R. H. Fischer, E. L. Giles and D. Coles, Trends Food Sci. Technol. , 2014, 40 , 211–225  CrossRef   CAS .
• V. J. Mohanraj and Y. Chen, Trop. J. Pharm. Res. , 2007, 5 , 561–573  Search PubMed .
• L. Stadler, M. Homafar, A. Hartl, S. Najafishirtari, R. Zbo, M. Petr, M. B. Gawande, J. Zhi and O. Reiser, ACS Sustainable Chem. Eng. , 2019, 7 , 2388–2399  CrossRef   CAS .
• M. D. Purkayastha and A. K. Manhar, Nanosci. Food Agri. , 2016, 2 , 59–128  Search PubMed .
• S. Chatterjee, Dhanurdhar and L. Rokhum, Renewable Sustainable Energy Rev. , 2017, 72 , 560–564  CrossRef   CAS .
• S. Bagheri and N. M. Julkapli, J. Magn. Magn. Mater. , 2016, 416 , 117–133  CrossRef   CAS .
• A. P. Ingle, A. Biswas, C. Vanlalveni, R. Lalfakzuala, I. Gupta, P. Ingle, L. Rokhum and M. Rai, Microb. Bionanotechnol. , 2020, 135–161  Search PubMed .
• C. Medina, M. J. Santos-Martinez, A. Radomski, O. I. Corrigan and M. W. Radomski, Br. J. Pharmacol. , 2007, 150 , 552–558  CrossRef   CAS .
• H. Deng, D. McShan, Y. Zhang, S. S. Sinha, Z. Arslan, P. C. Ray and H. Yu, Environ. Sci. Technol. , 2016, 50 , 8840–8848  CrossRef   CAS .
• C. Xu, O. U. Akakuru, J. Zheng and A. Wu, Front. Bioeng. Biotechnol. , 2019, 7 , 141  CrossRef .
• S. Bagheri, M. Yasemi, E. Safaie-Qamsari, J. Rashidiani, M. Abkar, M. Hassani, S. A. Mirhosseini and H. Kooshki, Artif. Cells, Nanomed., Biotechnol. , 2018, 46 , 462–471  CrossRef   CAS .
• A. Muthuraman, N. Rishitha and S. Mehdi, in Design of Nanostructures for Theranostics Applications , 2018, pp. 529–562  Search PubMed .
• S. Tortorella and T. C. Karagiannis, in Molecular Mechanisms and Physiology of Disease: Implications for Epigenetics and Health , 2014  Search PubMed .
• S. Ahmed, M. Ahmad, B. L. Swami and S. Ikram, J. Adv. Res. , 2016, 7 , 17–28  CrossRef   CAS .
• S. R. Vijayan, P. Santhiyagu, R. Ramasamy, P. Arivalagan, G. Kumar, K. Ethiraj and B. R. Ramaswamy, Enzyme Microb. Technol. , 2016, 95 , 45–57  CrossRef   CAS .
• S. Ahmed, Annu, S. Ikram and S. Yudha, J. Photochem. Photobiol., B , 2016, 161 , 141–153  CrossRef   CAS .
• P. Mohanpuria, N. K. Rana and S. K. Yadav, J. Nanopart. Res. , 2008, 10 , 507–517  CrossRef   CAS .
• G. Pathak, K. Rajkumari and L. Rokhum, Nanoscale Adv. , 2019, 1 , 1013–1020  RSC .
• S. A. Saiqa Ikram, J. Nanomed. Nanotechnol. , 2015, 6 , 1000309  CrossRef .
• S. Ahmed and S. Ikram, Nano Res. Appl. , 2015, 1 , 1–6  Search PubMed .
• K. Rajkumari, D. Das, G. Pathak and L. Rokhum, New J. Chem. , 2019, 43 , 2134–2140  RSC .
• B. Changmai, I. B. Laskar and L. Rokhum, J. Taiwan Inst. Chem. Eng. , 2019, 102 , 276–282  CrossRef   CAS .
• B. Changmai, P. Sudarsanam and L. Rokhum, Ind. Crops Prod. , 2020, 145 , 111911  CrossRef   CAS .
• B. Nath, B. Das, P. Kalita and S. Basumatary, J. Cleaner Prod. , 2019, 239 , 118112  CrossRef   CAS .
• S. Nour, N. Baheiraei, R. Imani, M. Khodaei, A. Alizadeh, N. Rabiee and S. M. Moazzeni, J. Mater. Sci.: Mater. Med. , 2019, 30 , 120  CrossRef .
• O. Bondarenko, K. Juganson, A. Ivask, K. Kasemets, M. Mortimer and A. Kahru, Arch. Toxicol. , 2013, 87 , 1181–1200  CrossRef   CAS .
• A. Pal, S. Shah and S. Devi, Mater. Chem. Phys. , 2009, 114 , 530–532  CrossRef   CAS .
• T. Wu, H. Shen, L. Sun, B. Cheng, B. Liu and J. Shen, ACS Appl. Mater. Interfaces , 2012, 4 , 2041–2047  CrossRef   CAS .
• X. Zhang, H. Sun, S. Tan, J. Gao, Y. Fu and Z. Liu, Inorg. Chem. Commun. , 2019, 100 , 44–50  CrossRef   CAS .
• V. R. Remya, V. K. Abitha, P. S. Rajput, A. V. Rane and A. Dutta, Chem. Int. , 2019, 3 , 165–171  Search PubMed .
• M. Rafique, I. Sadaf, M. S. Rafique and M. B. Tahir, Artif. Cells, Nanomed., Biotechnol. , 2017, 45 , 1272–1291  CrossRef   CAS .
• C. Vanlalveni, K. Rajkumari, A. Biswas, P. P. Adhikari, R. Lalfakzuala and L. Rokhum, Bionanoscience , 2018, 8 , 624–631  CrossRef .
• N. Durán, P. D. Marcato, G. I. H. De Souza, O. L. Alves and E. Esposito, J. Biomed. Nanotechnol. , 2007, 3 , 203–208  CrossRef .
• A. J. Kora, R. B. Sashidhar and J. Arunachalam, Carbohydr. Polym. , 2010, 82 , 670–679  CrossRef   CAS .
• A. Ahmad, Y. Wei, F. Syed, K. Tahir, A. U. Rehman, A. Khan, S. Ullah and Q. Yuan, Microb. Pathog. , 2017, 102 , 133–142  CrossRef   CAS .
• S. Sumitha, S. Vasanthi, S. Shalini, S. V. Chinni, S. C. B. Gopinath, P. Anbu, M. B. Bahari, R. Harish, S. Kathiresan and V. Ravichandran, Molecules , 2018, 23 , 3311  CrossRef .
• S. Vanaraj, B. B. Keerthana and K. Preethi, J. Inorg. Organomet. Polym. Mater. , 2017, 27 , 1412–1422  CrossRef   CAS .
• S. M. Ali, N. M. H. Yousef and N. A. Nafady, J. Nanomater. , 2015, 1–10  Search PubMed .
• V. Dhand, L. Soumya, S. Bharadwaj, S. Chakra, D. Bhatt and B. Sreedhar, Mater. Sci. Eng., C , 2016, 58 , 36–43  CrossRef   CAS .
• B. Ajitha, Y. Ashok Kumar Reddy, S. Shameer, K. M. Rajesh, Y. Suneetha and P. Sreedhara Reddy, J. Photochem. Photobiol., B , 2015, 194 , 84–92  CrossRef .
• R. Manikandan, B. Manikandan, T. Raman, K. Arunagirinathan, N. M. Prabhu, M. Jothi Basu, M. Perumal, S. Palanisamy and A. Munusamy, Spectrochim. Acta, Part A , 2015, 138 , 120–129  CrossRef   CAS .
• A. Biswas, C. Vanlalveni, P. P. Adhikari, R. Lalfakzuala and L. Rokhum, IET Nanobiotechnol. , 2018, 12 , 933–938  CrossRef .
• T. Kokila, P. S. Ramesh and D. Geetha, Appl. Nanosci. , 2015, 5 , 911–920  CrossRef   CAS .
• V. Kathiravan, S. Ravi, S. Ashokkumar, S. Velmurugan, K. Elumalai and C. P. Khatiwada, Spectrochim. Acta, Part A , 2015, 139 , 200–205  CrossRef   CAS .
• A. K. Jha, K. Prasad and A. R. Kulkarni, Colloids Surf., B , 2009, 71 , 226–229  CrossRef   CAS .
• N. Vigneshwaran, N. M. Ashtaputre, P. V. Varadarajan, R. P. Nachane, K. M. Paralikar and R. H. Balasubramanya, Mater. Lett. , 2007, 61 , 1413–1418  CrossRef   CAS .
• S. Shivaji, S. Madhu and S. Singh, Process Biochem. , 2011, 46 , 1800–1807  CrossRef   CAS .
• M. J. Ahmed, G. Murtaza, A. Mehmood and T. M. Bhatti, Mater. Lett. , 2015, 153 , 10–13  CrossRef   CAS .
• A. Miri, M. Sarani, M. Rezazade Bazaz and M. Darroudi, Spectrochim. Acta, Part A , 2015, 141 , 287–291  CrossRef   CAS .
• S. Medda, A. Hajra, U. Dey, P. Bose and N. K. Mondal, Appl. Nanosci. , 2014, 5 , 875–880  CrossRef .
• P. Premasudha, M. Venkataramana, M. Abirami, P. Vanathi, K. Krishna and R. Rajendran, Bull. Mater. Sci. , 2015, 38 , 965–973  CrossRef   CAS .
• B. Ajitha, Y. A. K. Reddy and P. S. Reddy, J. Photochem. Photobiol., B , 2015, 146 , 1–9  CrossRef   CAS .
• M. Kumara Swamy, K. M. Sudipta, K. Jayanta and S. Balasubramanya, Appl. Nanosci. , 2014, 5 , 73–81  CrossRef .
• S. R. Goswami, T. Sahareen, M. Singh and S. Kumar, J. Ind. Eng. Chem. , 2015, 26 , 73–80  CrossRef   CAS .
• M. Harshiny, M. Matheswaran, G. Arthanareeswaran, S. Kumaran and S. Rajasree, Ecotoxicol. Environ. Saf. , 2015, 121 , 135–141  CrossRef   CAS .
• N. Krithiga, A. Rajalakshmi and A. Jayachitra, J. Nanosci. , 2015, 1 , 128204  Search PubMed .
• S. S. Sana, V. R. Badineni, S. K. Arla and V. K. Naidu Boya, Mater. Lett. , 2015, 145 , 347–350  CrossRef   CAS .
• P. Velmurugan, M. Cho, S. S. Lim, S. K. Seo, H. Myung, K. S. Bang, S. Sivakumar, K. M. Cho and B. T. Oh, Mater. Lett. , 2015, 138 , 272–275  CrossRef   CAS .
• D. Bose and S. Chatterjee, Indian J. Microbiol. , 2015, 55 , 163–167  CrossRef   CAS .
• G. Marslin, R. K. Selvakesavan, G. Franklin, B. Sarmento and A. C. P. Dias, Int. J. Nanomed. , 2015, 10 , 5955–5963  CAS .
• B. Sadeghi, A. Rostami and S. S. Momeni, Spectrochim. Acta, Part A , 2015, 134 , 326–332  CrossRef   CAS .
• A. Devadiga, K. V. Shetty and M. B. Saidutta, Int. Nano Lett. , 2015, 5 , 205–214  CrossRef   CAS .
• R. K. Salar, P. Sharma and N. Kumar, Resour.-Effic. Technol. , 2015, 1 , 106–115  Search PubMed .
• A. Verma and M. S. Mehata, J. Radiat. Res. Appl. Sci. , 2016, 9 , 109–115  CrossRef   CAS .
• V. Ravichandran, S. Vasanthi, S. Shalini, S. Adnan and A. Shah, Mater. Lett. , 2016, 180 , 264–267  CrossRef   CAS .
• S. Ahmed, A. K. Manzoor and S. Ikram, J. Bionanosci. , 2016, 10 , 282–287  CrossRef   CAS .
• B. Sundararajan, G. Mahendran, R. Thamaraiselvi and B. D. Ranjitha Kumari, Bull. Mater. Sci. , 2016, 39 , 423–431  CrossRef   CAS .
• D. Bose and S. Chatterjee, Appl. Nanosci. , 2016, 6 , 895–901  CrossRef   CAS .
• Y. K. Mohanta, S. K. Panda, K. Biswas, A. Tamang, J. Bandyopadhyay, D. De, D. Mohanta and A. K. Bastia, IET Nanobiotechnol. , 2016, 10 , 438–444  CrossRef .
• C. S. Espenti, K. S. V. K. Rao and K. M. Rao, Mater. Lett. , 2016, 147 , 129–133  CrossRef .
• K. Anandalakshmi, J. Venugobal and V. Ramasamy, Appl. Nanosci. , 2016, 6 , 399–408  CrossRef   CAS .
• S. Ahmed, Saifullah, M. Ahmad, B. L. Swami and S. Ikram, J. Radiat. Res. Appl. Sci. , 2016, 9 , 1–7  CrossRef .
• K. Khanra, S. Panja, I. Choudhuri, A. Chakraborty and N. Bhattacharyya, Nanomed. J. , 2015, 7 , 128–133  CAS .
• J. L. López-Miranda, M. Vázquez, N. Fletes, R. Esparza and G. Rosas, Mater. Lett. , 2016, 176 , 285–289  CrossRef .
• K. Jyoti, M. Baunthiyal and A. Singh, J. Radiat. Res. Appl. Sci. , 2016, 9 , 217–227  CrossRef   CAS .
• S. Soman and J. G. Ray, J. Photochem. Photobiol., B , 2016, 163 , 391–402  CrossRef   CAS .
• B. Ajitha, Y. A. K. Reddy, P. S. Reddy, Y. Suneetha, H. J. Jeon and C. W. Ahn, J. Mol. Liq. , 2016, 219 , 474–481  CrossRef   CAS .
• D. McShan, Y. Zhang, H. Deng, P. C. Ray and H. Yu, J. Environ. Sci. Health, Part C: Environ. Carcinog. Ecotoxicol. Rev. , 2015, 33 , 369–384  CrossRef   CAS .
• V. P. Manjamadha and K. Muthukumar, Bioprocess Biosyst. Eng. , 2016, 39 , 401–411  CrossRef   CAS .
• N. Chauhan, A. K. Tyagi, P. Kumar and A. Malik, Front. Microbiol. , 2016, 7 , 1748  Search PubMed .
• D. K. Verma, S. H. Hasan and R. M. Banik, J. Photochem. Photobiol., B , 2016, 155 , 51–59  CrossRef   CAS .
• B. Ajitha, Y. Ashok Kumar Reddy, K. M. Rajesh and P. Sreedhara Reddy, Mater. Today: Proc. , 2016, 3 , 1977–1984  Search PubMed .
• G. Kuppurangan, B. Karuppasamy, K. Nagarajan, R. Krishnasamy Sekar, N. Viswaprakash and T. Ramasamy, Appl. Nanosci. , 2015, 6 , 973–982  CrossRef .
• A. R. Allafchian, S. Z. Mirahmadi-Zare, S. A. H. Jalali, S. S. Hashemi and M. R. Vahabi, J. Nanostruct. Chem. , 2016, 6 , 129–135  CrossRef   CAS .
• R. Kumari, G. Brahma, S. Rajak, M. Singh and S. Kumar, Orient. Pharm. Exp. Med. , 2016, 16 , 195–201  CrossRef .
• O. Azizian-Shermeh, A. Einali and A. Ghasemi, Adv. Powder Technol. , 2017, 28 , 3167–3171  Search PubMed .
• B. Bhuyan, A. Paul, B. Paul, S. S. Dhar and P. Dutta, J. Photochem. Photobiol., B , 2017, 173 , 210–215  CrossRef   CAS .
• S. Mahadevan, S. Vijayakumar and P. Arulmozhi, Microb. Pathog. , 2017, 113 , 445–450  CrossRef   CAS .
• E. E. Elemike, D. C. Onwudiwe, O. E. Fayemi, A. C. Ekennia, E. E. Ebenso and L. R. Tiedt, J. Cluster Sci. , 2016, 28 , 309–330  CrossRef .
• N. Soni and R. C. Dhiman, Chin. Herb. Med. , 2017, 9 , 289–294  CrossRef .
• Y. K. Mohanta, S. K. Panda, R. Jayabalan, N. Sharma, A. K. Bastia and T. K. Mohanta, Front. Mol. Biosci. , 2017, 4 , 14  Search PubMed .
• E. E. Elemike, D. C. Onwudiwe, A. C. Ekennia, R. C. Ehiri and N. J. Nnaji, Mater. Sci. Eng., C , 2017, 75 , 980–989  CrossRef   CAS .
• I. Ocsoy, A. Demirbas, E. S. McLamore, B. Altinsoy, N. Ildiz and A. Baldemir, J. Mol. Liq. , 2017, 238 , 263–269  CrossRef   CAS .
• H. S. A. Al-Shmgani, W. H. Mohammed, G. M. Sulaiman and A. H. Saadoon, Artif. Cells, Nanomed., Biotechnol. , 2016, 45 , 1234–1240,  DOI: 10.1080/21691401.2016.1220950 .
• K. Sahayaraj and S. Rajesh, Sci. against Microb. Pathog. Communicating Current Research and Technological Advances . 2011, vol. 23, pp. 228–244  Search PubMed .
• E. E. Elemike, D. C. Onwudiwe, A. C. Ekennia and L. Katata-Seru, Res. Chem. Intermed. , 2016, 43 , 1383–1394  CrossRef .
• S. V. Otari, S. H. Pawar, S. K. S. Patel, R. K. Singh, S. Y. Kim, J. H. Lee, L. Zhang and J. K. Lee, J. Microbiol. Biotechnol. , 2017, 27 , 731–738  CrossRef   CAS .
• T. Rasheed, M. Bilal, H. M. N. Iqbal and C. Li, Colloids Surf., B , 2017, 158 , 408–415  CrossRef   CAS .
• P. Thatoi, R. G. Kerry, S. Gouda, G. Das, K. Pramanik, H. Thatoi and J. K. Patra, J. Photochem. Photobiol., B , 2016, 163 , 311–318  CrossRef   CAS .
• L. Wang, Y. Wu, J. Xie, S. Wu and Z. Wu, Mater. Sci. Eng., C , 2018, 86 , 1–8  CrossRef   CAS .
• R. Geethalakshmi and D. V. L. Sarada, Ind. Crops Prod. , 2013, 51 , 107–115  CrossRef .
• R. G. Saratale, G. Benelli, G. Kumar, D. S. Kim and G. D. Saratale, Environ. Sci. Pollut. Res. , 2017, 25 , 10392–10406  CrossRef .
• A. Lateef, B. I. Folarin, S. M. Oladejo, P. O. Akinola, L. S. Beukes and E. B. Gueguim-Kana, Prep. Biochem. Biotechnol. , 2018, 1–7 , 1479864  Search PubMed .
• R. Vijayan, S. Joseph and B. Mathew, Part. Sci. Technol. , 2018, 1–11 , 1450312  Search PubMed .
• D. Kavaz, H. Umar and S. Shehu, Artif. Cells, Nanomed., Biotechnol. , 2019, 1–11 , 1536060  Search PubMed .
• F. Erci, R. Cakir-Koc and I. Isildak, Artif. Cells, Nanomed., Biotechnol. , 2017, 1–9 , 1415917  Search PubMed .
• S. Pal, Y. K. Tak and J. M. Song, Appl. Environ. Microbiol. , 2007, 73 , 1712–1720  CrossRef   CAS .
• R. Vijayan, S. Joseph and B. Mathew, Artif. Cells, Nanomed., Biotechnol. , 2017, 46 , 861–871  CrossRef .
• M. Kumari, S. Pandey, V. P. Giri, A. Bhattacharya, R. Shukla, A. Mishra and C. S. Nautiyal, Microb. Pathog. , 2017, 105 , 346–355  CrossRef   CAS .
• P. Kanmani and S. T. Lim, Process Biochem. , 2013, 48 , 1099–1106  CrossRef   CAS .
• V. K. Sharma, R. A. Yngard and Y. Lin, Adv. Colloid Interface Sci. , 2009, 145 , 83–96  CrossRef   CAS .
• A. Biswas and L. Rokhum, Int. Conf. Syst. Process. Physics, Chem. Biol. , 2018, pp. 1–7  Search PubMed .
• M. Baghayeri, B. Mahdavi, Z. Hosseinpor-Mohsen Abadi and S. Farhadi, Appl. Organomet. Chem. , 2017, 32 , e4057  Search PubMed .
• S. Ghotekar, A. Savale and S. Pansambal, J. Water Environ. Nanotechnol. , 2018, 3 , 95–105  CAS .
• A. Biswas, L. Chawngthu, C. Vanlalveni, R. Hnamte, R. Lalfakzuala and L. Rokhum, J. Bionanosci. , 2018, 12 , 227–232  CrossRef   CAS .
• N. Manosalva, G. Tortella, M. Cristina Diez, H. Schalchli, A. B. Seabra, N. Durán and O. Rubilar, World J. Microbiol. Biotechnol. , 2019, 35 , 1–9  CrossRef   CAS .
• S. Onitsuka, T. Hamada and H. Okamura, Colloids Surf., B , 2019, 173 , 242–248  CrossRef   CAS .
• E. Bernardo-Mazariegos, B. Valdez-Salas, D. González-Mendoza, A. Abdelmoteleb, O. Tzintzun Camacho, C. Ceceña Duran and F. Gutiérrez-Miceli, Rev. Argent. Microbiol. , 2019, 51 , 103–109  Search PubMed .
• K. Kanagamani, P. Muthukrishnan, K. Shankar, A. Kathiresan, H. Barabadi and M. Saravanan, J. Cluster Sci. , 2019, 30 , 1415–1424  CrossRef   CAS .
• S. Paosen, S. Jindapol, R. Soontarach and S. P. Voravuthikunchai, APMIS , 2019, 127 , 764–778  CrossRef   CAS .
• E. H. Ibrahim, M. Kilany, H. A. Ghramh, K. A. Khan and S. ul Islam, Saudi J. Biol. Sci. , 2019, 26 , 1689–1694  CrossRef   CAS .
• M. Nilavukkarasi, S. Vijayakumar and S. Prathip Kumar, Mater. Sci. Energy Technol. , 2020, 3 , 371–376  Search PubMed .
• Z. Shunying, Y. Yang, Y. Huaidong, Y. Yue and Z. Guolin, J. Ethnopharmacol. , 2005, 96 , 151–158  CrossRef .
• P. Moteriya and S. Chanda, J. Inorg. Organomet. Polym. Mater. , 2020, 30 , 3920–3932  CrossRef   CAS .
• W. Huang, M. Yan, H. Duan, Y. Bi, X. Cheng and H. Yu, J. Nanomater. , 2020, 1–7 , 9535432  Search PubMed .
• F. Ö. Küp, S. Çoşkunçay and F. Duman, Mater. Sci. Eng., C , 2020, 107 , 110207  CrossRef .
• M. A. Ramadan, A. E. Shawkey, M. A. Rabeh and A. O. Abdellatif, J. Herb. Med. , 2020, 20 , 100289  CrossRef .
• S. Javan bakht Dalir, H. Djahaniani, F. Nabati and M. Hekmati, Heliyon , 2020, 6 , e03624  CrossRef .
• R. K. Chahande, B. A. Mehere, P. K. Pantawane, P. B. Chouke and S. R. Murai, Mater. Today: Proc. , 2020, 29 , 923–928  CAS .
• S. A. Khan, S. Shahid and C. S. Lee, Biomolecules , 2020, 10 , 835  CrossRef   CAS .
• A. O. Nyabola, P. G. Kareru, E. S. Madivoli, S. I. Wanakai and E. G. Maina, J. Inorg. Organomet. Polym. Mater. , 2020, 30 , 3493–3501  CrossRef   CAS .
• S. Jebril, R. Khanfir Ben Jenana and C. Dridi, Mater. Chem. Phys. , 2020, 248 , 122898  CrossRef   CAS .
• R. Parvataneni, Drug Chem. Toxicol. , 2020, 43 , 307–321  CrossRef   CAS .
• E. S. Madivoli, P. G. Kareru, A. N. Gachanja, S. M. Mugo, D. S. Makhanu, S. I. Wanakai and Y. Gavamukulya, J. Inorg. Organomet. Polym. Mater. , 2020, 30 , 2842–2850  CrossRef   CAS .
• A. Biswas, C. Vanlalveni, P. P. Adhikari, R. Lalfakzuala and L. Rokhum, Micro Nano Lett. , 2019, 14 , 799–803  CrossRef   CAS .
• C. Vijilvani, M. R. Bindhu, F. C. Frincy, M. S. AlSalhi, S. Sabitha, K. Saravanakumar, S. Devanesan, M. Umadevi, M. J. Aljaafreh and M. Atif, J. Photochem. Photobiol., B , 2020, 202 , 111713  CrossRef   CAS .
• M. Maghimaa and S. Ali, J. Photochem. Photobiol., B , 2020, 204 , 111806  CrossRef   CAS .
• M. A. Asghar, E. Zahir, M. A. Asghar, J. Iqbal and A. A. Rehman, PLoS One , 2020, 15 , e0234964  CrossRef   CAS .
• B. Reidy, A. Haase, A. Luch, K. A. Dawson and I. Lynch, Materials , 2013, 6 , 2295–2350  CrossRef   CAS .
• A. A. Lourthuraj, M. M. Selvam, M. S. Hussain, A. W. A. Abdel-Warith, E. M. I. Younis and N. A. Al-Asgah, Saudi J. Biol. Sci. , 2020, 27 , 1753–1759  CrossRef   CAS .
• A. K. Keshari, R. Srivastava, P. Singh, V. B. Yadav and G. Nath, J. Ayurveda Integr. Med. , 2020, 11 , 37–44  CrossRef .
• A. J. Kora, J. Mounika and R. Jagadeeshwar, Fungal Biol. , 2020, 124 , 671–681  CrossRef   CAS .
• A. M. Elgorban, A. E. R. M. El-Samawaty, M. A. Yassin, S. R. Sayed, S. F. Adil, K. M. Elhindi, M. Bakri and M. Khan, Biotechnol. Biotechnol. Equip. , 2015, 30 , 56–62  CrossRef .
• A. Nouri, M. Tavakkoli Yaraki, A. Lajevardi, Z. Rezaei, M. Ghorbanpour and M. Tanzifi, Colloids Interface Sci. Commun. , 2020, 35 , 100252,  DOI: 10.1016/j.colcom.2020.100252 .
• M. Ghaedi, M. Yousefinejad, M. Safarpoor, H. Z. Khafri and M. K. Purkait, J. Ind. Eng. Chem. , 2015, 31 , 167–172  CrossRef   CAS .
• S. Muthukrishnan, S. Bhakya, T. Senthil Kumar and M. V. Rao, Ind. Crops Prod. , 2015, 63 , 119–124  CrossRef   CAS .
• N. L. Gavade, A. N. Kadam, M. B. Suwarnkar, V. P. Ghodake and K. M. Garadkar, Spectrochim. Acta, Part A , 2015, 136 , 953–960  CrossRef   CAS .
• T. J. I. Edison and M. G. Sethuraman, Process Biochem. , 2012, 47 , 1351–1357  CrossRef   CAS .
• R. Vivek, R. Thangam, K. Muthuchelian, P. Gunasekaran, K. Kaveri and S. Kannan, Process Biochem. , 2012, 47 , 2405–2410  CrossRef   CAS .
• Y. Sun, Y. Yin, B. T. Mayers, T. Herricks and Y. Xia, Chem. Mater. , 2002, 14 , 4736–4745  CrossRef   CAS .
• R. M. Gengan, K. Anand, A. Phulukdaree and A. Chuturgoon, Colloids Surf., B , 2013, 105 , 87–91  CrossRef   CAS .
• P. Logeswari, S. Silambarasan and J. Abraham, J. Saudi Chem. Soc. , 2015, 19 , 311–317  CrossRef .
• H. Kolya, P. Maiti, A. Pandey and T. Tripathy, J. Anal. Sci. Technol. , 2015, 6 , 33  CrossRef .
• S. N. Sinha and D. Paul, Spectrosc. Lett. , 2015, 48 , 600–604  CrossRef   CAS .
• X. Yao, M. Jericho, D. Pink and T. Beveridge, J. Bacteriol. , 1999, 181 , 6865–6875  CrossRef   CAS .
• K. Elangovan, D. Elumalai, S. Anupriya, R. Shenbhagaraman, P. K. Kaleena and K. Murugesan, J. Photochem. Photobiol., B , 2015, 151 , 118–124  CrossRef   CAS .
• S. B. Ulaeto, G. M. Mathew, J. K. Pancrecious, J. B. Nair, T. P. D. Rajan, K. K. Maiti and B. C. Pai, ACS Biomater. Sci. Eng. , 2020, 6 , 235–245  CrossRef   CAS .
• B. Ajitha, Y. A. K. Reddy, H. J. Jeon and C. W. Ahn, Adv. Powder Technol. , 2018, 29 , 86–93  CrossRef   CAS .
• M. Khatami, S. Pourseyedi, M. Khatami, H. Hamidi, M. Zaeifi and L. Soltani, Bioresour. Bioprocess. , 2015, 2 , 19  CrossRef .
• H. Xu, L. Wang, H. Su, L. Gu, T. Han, F. Meng and C. Liu, Food Biophys. , 2014, 10 , 12–18  CrossRef .
• M. S. Alsalhi, S. Devanesan, A. A. Alfuraydi, R. Vishnubalaji, M. A. Munusamy, K. Murugan, M. Nicoletti and G. Benelli, Int. J. Nanomed. , 2016, 11 , 4439–4449  CrossRef   CAS .
• A. Lateef, M. A. Akande, M. A. Azeez, S. A. Ojo, B. I. Folarin, E. B. Gueguim-Kana and L. S. Beukes, Nanotechnol. Rev. , 2016, 5 , 507–520  CAS .
• M. K. Choudhary, J. Kataria, S. S. Cameotra and J. Singh, Appl. Nanosci. , 2016, 6 , 105–111  CrossRef   CAS .
• Z. H. Pak, H. Abbaspour, N. Karimi and A. Fattahi, Appl. Sci. , 2016, 6 , 69  CrossRef .
• M. Khatami, M. S. Nejad, S. Salari and P. G. N. Almani, IET Nanobiotechnol. , 2016, 10 , 237–243  CrossRef .
• M. Khatami, R. Mehnipor, M. H. S. Poor and G. S. Jouzani, J. Cluster Sci. , 2016, 27 , 1601–1612  CrossRef   CAS .
• A. Chahardoli, N. Karimi and A. Fattahi, Iran. J. Pharm. Res. , 2017, 16 , 1167–1175  Search PubMed .
• M. T. Haseeb, M. A. Hussain, K. Abbas, B. G. M. Youssif, S. Bashir, S. H. Yuk and S. N. A. Bukhari, Int. J. Nanomed. , 2017, 12 , 2845–2855  CrossRef   CAS .
• M. Dhayalan, M. I. J. Denison, L. Anitha Jegadeeshwari, K. Krishnan and N. Nagendra Gandhi, Nat. Prod. Res. , 2016, 31 , 465–468  CrossRef .
• S. Pirtarighat, M. Ghannadnia and S. Baghshahi, Nanomed. J. , 2017, 4 , 184–190  CAS .
• R. Kumar, P. Sharma, A. Bamal, S. Negi and S. Chaudhary, Green Process. Synth. , 2017, 6 , 0146  Search PubMed .
• Y. He, F. Wei, Z. Ma, H. Zhang, Q. Yang, B. Yao, Z. Huang, J. Li, C. Zeng and Q. Zhang, RSC Adv. , 2017, 7 , 39842–39851  RSC .
• S. Balakrishnan, I. Sivaji, S. Kandasamy, S. Duraisamy, N. S. Kumar and G. Gurusubramanian, Environ. Sci. Pollut. Res. , 2017, 24 , 14758–14769  CrossRef   CAS .
• A. Qidwai, R. Kumar and A. Dikshit, Green Chem. Lett. Rev. , 2018, 11 , 176–188  CrossRef   CAS .
• M. A. Ansari and M. A. Alzohairy, J. Evidence-Based Complementary Altern. Med. , 2018, 1–9 , 1860280  Search PubMed .
• A. Rautela, J. Rani and M. Debnath, J. Anal. Sci. Technol. , 2019, 10 , 1–10  CrossRef .
• N. G. Girón-Vázquez, C. M. Gómez-Gutiérrez, C. A. Soto-Robles, O. Nava, E. Lugo-Medina, V. H. Castrejón-Sánchez, A. R. Vilchis-Nestor and P. A. Luque, Results Phys. , 2019, 13 , 102142  CrossRef .
• L. Hernández-Morales, H. Espinoza-Gómez, L. Z. Flores-López, E. L. Sotelo-Barrera, A. Núñez-Rivera, R. D. Cadena-Nava, G. Alonso-Núñez and K. A. Espinoza, Appl. Surf. Sci. , 2019, 489 , 952–961  CrossRef .
• R. Varghese, M. A. Almalki, S. Ilavenil, J. Rebecca and K. C. Choi, Saudi J. Biol. Sci. , 2019, 26 , 148–154  CrossRef   CAS .
• S. Arokiyaraj, S. H. Choi, Y. Lee, R. Bharanidharan, V. I. Hairul-Islam, B. Vijayakumar, Y. K. Oh, V. Dinesh-Kumar, S. Vincent and K. H. Kim, Molecules , 2015, 20 , 384–395  CrossRef .
• M. Adnan, M. Obyedul Kalam Azad, A. Madhusudhan, K. Saravanakumar, X. Hu, M. H. Wang and C. D. Ha, Nanotechnology , 2020, 31 , 26  CrossRef .
• F. A. Qais, A. Shafiq, I. Ahmad, F. M. Husain, R. A. Khan and I. Hassan, Microb. Pathog. , 2020, 144 , 104172  CrossRef .
• M. F. Zayed, R. A. Mahfoze, S. M. El-kousy and E. A. Al-Ashkar, Colloids Surf., A , 2020, 585 , 124167  CrossRef   CAS .
• J. H. Kim, J. Chromatogr. B: Anal. Technol. Biomed. Life Sci. , 2017, 1063 , 196–203  CrossRef   CAS .
• T. Belwal, P. Dhyani, I. D. Bhatt, R. S. Rawal and V. Pande, Food Chem. , 2016, 207 , 115–124  CrossRef .
• H. Padalia, P. Moteriya and S. Chanda, Arabian J. Chem. , 2015, 8 , 732–741  CrossRef   CAS .
• N. Gogoi, P. J. Babu, C. Mahanta and U. Bora, Mater. Sci. Eng., C , 2015, 46 , 463–469  CrossRef   CAS .
• P. Moteriya and S. Chanda, Artif. Cells, Nanomed., Biotechnol. , 2016, 45 , 1556–1567  CrossRef .
• A. Ebrahiminezhad, Y. Barzegar, Y. Ghasemi and A. Berenjian, Chem. Ind. Chem. Eng. Q. , 2017, 232 , 31–37  CrossRef .
• N. Chandrasekhar and S. P. Vinay, Appl. Nanosci. , 2017, 7 , 851–861  CrossRef   CAS .
• M. Hariram, S. Vivekanandhan, V. Ganesan, S. Muthuramkumar, A. Rodriguez-uribe, A. K. Mohanty and M. Misra, Bioresour. Technol. Rep. , 2019, 7 , 100298  CrossRef .
• M. R. Bindhu, M. Umadevi, G. A. Esmail, N. A. Al-Dhabi and M. V. Arasu, J. Photochem. Photobiol., B , 2020, 205 , 111836  CrossRef   CAS .
• B. Ajitha, Y. A. K. Reddy, Y. Lee, M. J. Kim and C. W. Ahn, Appl. Organomet. Chem. , 2019, 33 , e4867  CrossRef .
• A. K. Mittal, D. Tripathy, A. Choudhary, P. K. Aili, A. Chatterjee, I. P. Singh and U. C. Banerjee, Mater. Sci. Eng., C , 2015, 53 , 120–127  CrossRef   CAS .
• S. Pugazhendhi, E. Kirubha, P. K. Palanisamy and R. Gopalakrishnan, Appl. Surf. Sci. , 2015, 357 , 1801–1808  CrossRef   CAS .
• P. R. Rathi Sre, M. Reka, R. Poovazhagi, M. Arul Kumar and K. Murugesan, Spectrochim. Acta, Part A , 2015, 135 , 1137–1144  CrossRef   CAS .
• N. H. Rao, N. Lakshmidevi, S. V. N. Pammi, P. Kollu, S. Ganapaty and P. Lakshmi, Mater. Sci. Eng., C , 2016, 62 , 553–557  CrossRef   CAS .
• L. Pethakamsetty, K. Kothapenta, H. R. Nammi, L. K. Ruddaraju, P. Kollu, S. G. Yoon and S. V. N. Pammi, J. Environ. Sci. , 2017, 55 , 157–163  CrossRef   CAS .
• K. M. Ezealisiji, X. S. Noundou and S. E. Ukwueze, Appl. Nanosci. , 2017, 7 , 905–911  CrossRef   CAS .
• D. Wang, J. Markus, C. Wang, Y. J. Kim, R. Mathiyalagan, V. C. Aceituno, S. Ahn and D. C. Yang, Artif. Cells, Nanomed., Biotechnol. , 2016, 45 , 1548–1555  CrossRef .
• S. Kantipudi, L. Pethakamsetty, S. M. Kollana, J. R. Sunkara, P. Kollu, N. R. Parine, M. Rallabhandi and S. V. N. Pammi, IET Nanobiotechnol. , 2018, 12 , 133–137  CrossRef .
• G. Şeker Karatoprak, G. Aydin, B. Altinsoy, C. Altinkaynak, M. Koşar and I. Ocsoy, Enzyme Microb. Technol. , 2017, 97 , 21–26  CrossRef .
• S. Arokiyaraj, S. Vincent, M. Saravanan, Y. Lee, Y. K. Oh and K. H. Kim, Artif. Cells, Nanomed., Biotechnol. , 2016, 45 , 372–379  CrossRef .
• E. F. P. Henie, H. Zaiton and M. Suhaila, Int. Food Res. J. , 2009, 16 , 297–311  Search PubMed .
• F. Benakashani, A. Allafchian and S. A. H. Jalali, Green Chem. Lett. Rev. , 2017, 10 , 324–330  CrossRef   CAS .
• J. Markus, D. Wang, Y. J. Kim, S. Ahn, R. Mathiyalagan, C. Wang and D. C. Yang, Nanoscale Res. Lett. , 2017, 12 , 46  CrossRef .
• M. Oves, M. Aslam, M. A. Rauf, S. Qayyum, H. A. Qari, M. S. Khan, M. Z. Alam, S. Tabrez, A. Pugazhendhi and I. M. I. Ismail, Mater. Sci. Eng., C , 2018, 89 , 429–443  CrossRef   CAS .
• T. T. N. Nguyen, T. T. Vo, B. N. H. Nguyen, D. T. Nguyen, V. S. Dang, C. H. Dang and T. D. Nguyen, Environ. Sci. Pollut. Res. , 2018, 25 , 34247–34261  CrossRef   CAS .
• P. P. N. Vijay Kumar, R. L. Kalyani, S. C. Veerla, P. Kollu, U. Shameem and S. V. N. Pammi, Mater. Res. Express , 2019, 6 , 10  Search PubMed .
• D. Garibo, H. A. Borbón-Nuñez, J. N. D. de León, E. García Mendoza, I. Estrada, Y. Toledano-Magaña, H. Tiznado, M. Ovalle-Marroquin, A. G. Soto-Ramos, A. Blanco, J. A. Rodríguez, O. A. Romo, L. A. Chávez-Almazán and A. Susarrey-Arce, Sci. Rep. , 2020, 10 , 12805  CrossRef   CAS .
• M. N. Khan, T. A. Khan, Z. Khan and S. A. AL-Thabaiti, Bioprocess Biosyst. Eng. , 2015, 38 , 2397–2416  CrossRef   CAS .
• A. A. Alfuraydi, S. Devanesan, M. Al-Ansari, M. S. AlSalhi and A. J. Ranjitsingh, J. Photochem. Photobiol., B , 2019, 192 , 83–89  CrossRef   CAS .
• P. S. Ramesh, T. Kokila and D. Geetha, Spectrochim. Acta, Part A , 2015, 142 , 339–343  CrossRef   CAS .
• S. Lokina, A. Stephen, V. Kaviyarasan, C. Arulvasu and V. Narayanan, Synth. React. Inorg., Met.-Org., Nano-Met. Chem. , 2013, 45 , 37–41  Search PubMed .
• S. J. Mane Gavade, G. H. Nikam, R. S. Dhabbe, S. R. Sabale, B. V. Tamhankar and G. N. Mulik, Adv. Nat. Sci.: Nanosci. Nanotechnol. , 2015, 6 , 045015  Search PubMed .
• N. Mapara, M. Sharma, V. Shriram, R. Bharadwaj, K. C. Mohite and V. Kumar, Appl. Microbiol. Biotechnol. , 2015, 99 , 10655–10667  CrossRef   CAS .
• M. Ramar, B. Manikandan, P. N. Marimuthu, T. Raman, A. Mahalingam, P. Subramanian, S. Karthick and A. Munusamy, Spectrochim. Acta, Part A , 2015, 140 , 223–228  CrossRef   CAS .
• S. A. A. L. Rahisuddin, Z. Khan and N. Manzoor, Bioprocess Biosyst. Eng. , 2015, 38 , 1773–1781  CrossRef   CAS .
• P. Yugandhar and N. Savithramma, Appl. Nanosci. , 2015, 6 , 223–233  CrossRef .
• G. Mahendran and B. D. Ranjitha Kumari, Food Sci. Hum. Well. , 2016, 5 , 207–218  CrossRef .
• P. Mosae Selvakumar, C. A. Antonyraj, R. Babu, A. Dakhsinamurthy, N. Manikandan and A. Palanivel, Synth. React. Inorg., Met.-Org., Nano-Met. Chem. , 2015, 46 , 291–294  CrossRef .
• Z. A. Ali, R. Yahya, S. D. Sekaran and R. Puteh, Adv. Mater. Sci. Eng. , 2016, 2016 , 4102196  Search PubMed .
• C. M. K. Kumar, P. Yugandhar and N. Savithramma, J. Intercult. Ethnopharmacol. , 2017, 6 , 296–310  CrossRef .
• M. M. O. Rashid, K. N. Akhter, J. A. Chowdhury, F. Hossen, M. S. Hussain and M. T. Hossain, BMC Complementary Altern. Med. , 2017, 17 , 336  CrossRef .
• N. Jayaprakash, J. J. Vijaya, K. Kaviyarasu, K. Kombaiah, L. J. Kennedy, R. J. Ramalingam, M. A. Munusamy and H. A. Al-Lohedan, J. Photochem. Photobiol., B , 2017, 169 , 178–185  CrossRef   CAS .
• S. Farhadi, B. Ajerloo and A. Mohammadi, Acta Chim. Slov. , 2017, 67 , 1  Search PubMed .
• S. A. Umoren, A. M. Nzila, S. Sankaran, M. M. Solomon and P. S. Umoren, Pol. J. Chem. Technol. , 2017, 19 , 128–136  CAS .
• Z. E. Jiménez Pérez, R. Mathiyalagan, J. Markus, Y. J. Kim, H. M. Kang, R. Abbai, K. H. Seo, D. Wang, V. Soshnikova and D. C. Yang, Int. J. Nanomed. , 2017, 12 , 709–723  CrossRef .
• B. A. Providence, A. A. Chinyere, A. A. Ayi, O. O. Charles, T. A. Elijah and H. L. Ayomide, Int. J. Phys. Sci. , 2018, 13 , 24–32  CrossRef .
• K. H. Oh, V. Soshnikova, J. Markus, Y. J. Kim, S. C. Lee, P. Singh, V. Castro-Aceituno, S. Ahn, D. H. Kim, Y. J. Shim, Y. J. Kim and D. C. Yang, Artif. Cells, Nanomed., Biotechnol. , 2017, 46 , 599–606  CrossRef .
• T. Sowmyya and G. Vijaya Lakshmi, Bionanoscience , 2017, 8 , 179–195  Search PubMed .
• R. Dobrucka, M. Kaczmarek and J. Dlugaszewska, Adv. Nat. Sci.: Nanosci. Nanotechnol. , 2018, 9 , 025015  Search PubMed .
• G. M. Sangaonkar and K. D. Pawar, Colloids Surf., B , 2018, 164 , 210–217  CrossRef   CAS .
• N. Joshi, N. Jain, A. Pathak, J. Singh, R. Prasad and C. P. Upadhyaya, J. Sol-Gel Sci. Technol. , 2018, 86 , 682–689  CrossRef   CAS .
• S. Batool, Z. Hussain, M. B. K. Niazi, U. Liaqat and M. Afzal, J. Drug Delivery Sci. Technol. , 2019, 52 , 403–414  CrossRef   CAS .
• S. Andra, S. Balu, R. Ramoorthy, M. Muthalagu and V. S. Manisha, Mater. Today: Proc. , 2019, 9 , 639–644  CAS .
• F. K. Saidu, A. Mathew, A. Parveen, V. Valiyathra and G. V. Thomas, SN Appl. Sci. , 2019, 1 , 1368  CrossRef .
• M. I. Masum, M. M. Siddiqa, K. A. Ali, Y. Zhang, Y. Abdallah, E. Ibrahim, W. Qiu, C. Yan and B. Li, Front. Microbiol. , 2019, 10 , 820  CrossRef .
• J. Du, Z. Hu, Z. Yu, H. Li, J. Pan, D. Zhao and Y. Bai, Mater. Sci. Eng., C , 2019, 102 , 247–253  CrossRef   CAS .
• F. Gulbagca, S. Ozdemir, M. Gulcan and F. Sen, Heliyon , 2019, 5 , e02980  CrossRef .
• C. Vishwasrao, B. Momin and L. Ananthanarayan, Waste Biomass Valorization , 2018, 10 , 8  Search PubMed .
• M. M. R. Mollick, D. Rana, S. K. Dash, S. Chattopadhyay, B. Bhowmick, D. Maity, D. Mondal, S. Pattanayak, S. Roy, M. Chakraborty and D. Chattopadhyay, Arabian J. Chem. , 2019, 12 , 2572–2584,  DOI: 10.1016/j.arabjc.2015.04.033 .
• R. Renuka, K. R. Devi, M. Sivakami, T. Thilagavathi, R. Uthrakumar and K. Kaviyarasu, Biocatal. Agric. Biotechnol. , 2020, 24 , 101567  CrossRef .
• M. Devi, S. Devi, V. Sharma, N. Rana, R. K. Bhatia and A. K. Bhatt, J. Tradit. Complement. Med. , 2020, 10 , 158–165  CrossRef .
• M. A. Odeniyi, V. C. Okumah, B. C. Adebayo-Tayo and O. A. Odeniyi, Sustainable Chem. Pharm. , 2020, 15 , 100197  CrossRef .
• D. Sasidharan, T. R. Namitha, S. P. Johnson, V. Jose and P. Mathew, Sustainable Chem. Pharm. , 2020, 16 , 100255  CrossRef .
• T. Shankar, P. Karthiga, K. Swarnalatha and K. Rajkumar, Resour.-Effic. Technol. , 2017, 3 , 303–308  Search PubMed .
• S. P. Vinay and N. Chandrasekhar, Mater. Today: Proc. , 2019, 9 , 499–505  CAS .
• P. Velusamy, J. Das, R. Pachaiappan, B. Vaseeharan and K. Pandian, Ind. Crops Prod. , 2015, 66 , 103–109  CrossRef   CAS .
• I. Murali Krishna, G. Bhagavanth Reddy, G. Veerabhadram and A. Madhusudhan, Appl. Nanosci. , 2015, 6 , 681–689  CrossRef .
• J. Du, H. Singh and T. H. Yi, Bioprocess Biosyst. Eng. , 2016, 39 , 1923–1931  CrossRef   CAS .
• A. C. d. J. Oliveira, A. R. de Araújo, P. V. Quelemes, D. Nadvorny, J. L. Soares-Sobrinho, J. R. S. d. A. Leite, E. C. da Silva-Filho and D. A. da Silva, Carbohydr. Polym. , 2019, 213 , 176–183  CrossRef   CAS .
• A. V. Samrot, J. L. A. Angalene, S. M. Roshini, P. Raji, S. M. Stefi, R. Preethi, A. J. Selvarani and A. Madankumar, J. Cluster Sci. , 2019, 30 , 1599–1610  CrossRef   CAS .
• M. Z. Siddiqui, A. R. Chowdhury, B. R. Singh, S. Maurya and N. Prasad, Natl. Acad. Sci. Lett. , 2020  DOI: 10.1007/s40009-020-00982-4 .
• A. Mumtaz, H. Munir, M. T. Zubair and M. H. Arif, Mater. Res. Express , 2019, 6 , 105308  CrossRef   CAS .
• C. A. Eric, V. Benjamín, C. Monica, A. C. Mario, D. M. Francisco, A. R. Rogelio, R. Navor and M. B. Jose, Afr. J. Biotechnol. , 2017, 16 , 400–407  CrossRef .
• M. Khatami, I. Sharifi, M. A. L. Nobre, N. Zafarnia and M. R. Aflatoonian, Green Chem. Lett. Rev. , 2018, 11 , 125–134  CrossRef   CAS .
• V. Ahluwalia, S. Elumalai, V. Kumar, S. Kumar and R. S. Sangwan, Microb. Pathog. , 2018, 114 , 402–408  CrossRef   CAS .
• P. Moteriya and S. Chanda, J. Genet. Eng. Biotechnol. , 2018, 16 , 105–113  CrossRef .
• P. Karthiga, Biotechnol. Res. Innov. , 2018, 2 , 30–36  CrossRef .
• F. Zandpour, A. R. Allafchian, M. R. Vahabi and S. A. H. Jalali, IET Nanobiotechnol. , 2018, 12 , 491–495  CrossRef .
• M. Cakić, S. Glišić, D. Cvetković, M. Cvetinov, L. Stanojević, B. Danilović and K. Cakić, Colloid J. , 2018, 80 , 803–813  CrossRef .
• S. Dehghanizade, J. Arasteh and A. Mirzaie, Artif. Cells, Nanomed., Biotechnol. , 2017, 46 , 160–168  CrossRef .
• M. Moyo, M. Gomba and T. Nharingo, Int. J. Ind. Chem. , 2015, 6 , 329–338  CrossRef   CAS .
• P. Yugandhar, R. Haribabu and N. Savithramma, 3 Biotech , 2015, 5 , 1031–1039  CrossRef .
• A. Sasikala, M. Linga Rao, N. Savithramma and T. N. V. K. V. Prasad, Appl. Nanosci. , 2014, 5 , 827–835  CrossRef .
• D. Nayak, S. Ashe, P. R. Rauta, M. Kumari and B. Nayak, Mater. Sci. Eng., C , 2016, 58 , 44–52  CrossRef   CAS .
• S. Priya Velammal, T. A. Devi and T. P. Amaladhas, J. Nanostruct. Chem. , 2016, 6 , 247–260  CrossRef .
• S. Bhakya, S. Muthukrishnan, M. Sukumaran, M. Grijalva, L. Cumbal, J. F. Benjamin and M. V. Rao, RSC Adv. , 2016, 6 , 81436–81446  RSC .
• Q. Ahmed, N. Gupta, A. Kumar and S. Nimesh, Artif. Cells, Nanomed., Biotechnol. , 2016, 45 , 1192–1200  CrossRef .
• S. Pattanayak, M. Rahaman, D. Maity, S. Chakraborty, S. Kumar and S. Chattopadhyay, J. Saudi Chem. Soc. , 2017, 21 , 673–684  CrossRef   CAS .
• G. Arya, R. M. Kumari, N. Gupta, A. Kumar and S. Nimesh, Artif. Cells, Nanomed., Biotechnol. , 2017, 1–9  Search PubMed .
• P. Karthiga, S. Rajeshkumar and G. Annadurai, J. Cluster Sci. , 2018, 29 , 1233–1241  CrossRef   CAS .
• S. Ramanathan, S. C. B. Gopinath, P. Anbu, T. Lakshmipriya, F. H. Kasim and C. G. Lee, J. Mol. Struct. , 2018, 1160 , 80–91  CrossRef   CAS .
• M. Das and S. S. Smita, Appl. Nanosci. , 2018, 8 , 1059–1067  CrossRef   CAS .
• E. C. Sekhar, K. S. V. K. Rao, K. M. S. Rao and S. B. Alisha, J. Appl. Pharm. Sci. , 2018, 8 , 1  Search PubMed .
• D. Bharathi, M. Diviya Josebin, S. Vasantharaj and V. Bhuvaneshwari, J. Nanostruct. Chem. , 2018, 8 , 83–92  CrossRef   CAS .
• R. P. Illanes Tormena, E. V. Rosa, B. d. F. Oliveira Mota, J. A. Chaker, C. W. Fagg, D. O. Freire, P. M. Martins, I. C. Rodrigues da Silva and M. H. Sousa, RSC Adv. , 2020, 10 , 20676–20681  RSC .
• A.-R. Phull, Q. Abbas, A. Ali, H. Raza, S. J. kim, M. Zia and I. Haq, Future J. Pharm. Sci. , 2016, 2 , 31–36  CrossRef .
• J. H. Lee, J. M. Lim, P. Velmurugan, Y. J. Park, Y. J. Park, K. S. Bang and B. T. Oh, J. Photochem. Photobiol., B , 2016, 162 , 93–99  CrossRef   CAS .
• G. Sharma, J. S. Nam, A. R. Sharma and S. S. Lee, Molecules , 2018, 23 , 2268  CrossRef .
• F. K. Alsammarraie, W. Wang, P. Zhou, A. Mustapha and M. Lin, Colloids Surf., B , 2018, 171 , 398–405  CrossRef   CAS .
• N. T. Selvi, R. Navamathavan, H. Y. Kim and R. Nirmala, Macromol. Res. , 2019, 27 , 1155–1160  CrossRef   CAS .
• S. Devanesan, K. Ponmurugan, M. S. AlSalhi and N. A. Al-Dhabi, Int. J. Nanomed. , 2020, 15 , 4351–4362  CrossRef   CAS .
• Y. Nan, L. I. Fuyan, J. Tiancai, L. I. U. Chongchong, S. U. N. Hushan, W. Lei and X. U. Hui, Acta Oceanol. Sin. , 2017, 36 , 95–100  Search PubMed .
• H. M. M. Ibrahim, J. Radiat. Res. Appl. Sci. , 2015, 8 , 265–275  CrossRef .
• J. Balavijayalakshmi and V. Ramalakshmi, J. Appl. Res. Technol. , 2017, 15 , 413–422  CrossRef .
• C. H. N. de Barros, G. C. F. Cruz, W. Mayrink and L. Tasic, Nanotechnol., Sci. Appl. , 2018, 11 , 1–14  CrossRef   CAS .
• C. Huo, M. Khoshnamvand, P. Liu, C. G. Yuan and W. Cao, Mater. Res. Express , 2018, 6 , 1  Search PubMed .
• M. Annu, S. Ahmed, G. Kaur, P. Sharma, S. Singh and S. Ikram, Toxicol. Res. , 2018, 7 , 923–930  CrossRef .
• R. G. Saratale, H. S. Shin, G. Kumar, G. Benelli, G. S. Ghodake, Y. Y. Jiang, D. S. Kim and G. D. Saratale, Environ. Sci. Pollut. Res. , 2017, 25 , 10250–10263  CrossRef .
• R. K. Das and D. Bhuyan, Nanotechnol. Environ. Eng. , 2019, 4 , 1  CrossRef .
• T. Dutta, N. N. Ghosh, M. Das, R. Adhikary, V. Mandal and A. P. Chattopadhyay, J. Environ. Chem. Eng. , 2020, 8 , 104019  CrossRef   CAS .
• E. Z. Gomaa, J. Genet. Eng. Biotechnol. , 2017, 15 , 49–57  CrossRef .
• A. Aravinthan, M. Govarthanan, K. Selvam, L. Praburaman, T. Selvankumar, R. Balamurugan, S. Kamala-Kannan and J. H. Kim, Int. J. Nanomed. , 2015, 10 , 1977–1983  CAS .
• S. Pugazhendhi, P. Sathya, P. K. Palanisamy and R. Gopalakrishnan, J. Photochem. Photobiol., B , 2016, 159 , 155–160  CrossRef   CAS .
• M. Mosaviniya, T. Kikhavani, M. Tanzifi, M. Tavakkoli Yaraki, P. Tajbakhsh and A. Lajevardi, Colloids Interface Sci. Commun. , 2019, 33 , 100211  CrossRef   CAS .
• M. Saha and P. K. Bandyopadhyay, Proc. Zool. Soc. , 2019, 72 , 180–186  CrossRef .
• S. Rajesh, V. Dharanishanthi and A. V. Kanna, J. Exp. Nanosci. , 2014, 10 , 1143–1152  CrossRef .
• P. Kuppusamy, S. J. A. Ichwan, N. R. Parine, M. M. Yusoff, G. P. Maniam and N. Govindan, J. Environ. Sci. , 2015, 29 , 151–157  CrossRef   CAS .
• U. Ramaswamy, D. Mukundan, A. Sreekumar and V. Mani, Mater. Today: Proc. , 2015, 2 , 4600–4608  Search PubMed .
• S. Salehi, S. A. S. Shandiz, F. Ghanbar, M. R. Darvish, M. S. Ardestani, A. Mirzaie and M. Jafari, Int. J. Nanomed. , 2016, 11 , 1835–1846  CAS .
• S. Anjum and B. H. Abbasi, Int. J. Nanomed. , 2016, 11 , 715–728  CrossRef   CAS .
• S. Ali, S. Perveen, M. Ali, T. Jiao, A. S. Sharma, H. Hassan, S. Devaraj, H. Li and Q. Chen, Mater. Sci. Eng., C , 2020, 108 , 110421  CrossRef   CAS .
• P. N. V. K. Pallela, S. Ummey, L. K. Ruddaraju, S. V. N. Pammi and S. G. Yoon, Microb. Pathog. , 2018, 124 , 63–69  CrossRef   CAS .
• M. Idrees, S. Batool, T. Kalsoom, S. Raina, H. M. A. Sharif and S. Yasmeen, Environ. Technol. , 2019, 40 , 1071–1078  CrossRef   CAS .
• A. Aygün, F. Gülbağça, M. S. Nas, M. H. Alma, M. H. Çalımlı, B. Ustaoglu, Y. C. Altunoglu, M. C. Baloğlu, K. Cellat and F. Şen, J. Pharm. Biomed. Anal. , 2020, 179 , 113012  CrossRef .
• R. R. Chavan, S. D. Bhinge, M. A. Bhutkar, D. S. Randive, G. H. Wadkar, S. S. Todkar and M. N. Urade, Mater. Today Commun. , 2020, 24 , 101320  CrossRef   CAS .
• R. Dobrucka and J. Długaszewska, Indian J. Microbiol. , 2015, 55 , 168–174  CrossRef   CAS .
• K. Jadhav, D. Dhamecha, B. Dalvi and M. Patil, Part. Sci. Technol. , 2015, 33 , 445–455  CrossRef   CAS .
• A. T. Shah, M. I. Din, S. Bashir, M. A. Qadir and F. Rashid, Anal. Lett. , 2015, 48 , 1180–1189  CrossRef   CAS .
• D. Nayak, S. Ashe, P. R. Rauta and B. Nayak, IET Nanobiotechnol. , 2015, 9 , 288–293  CrossRef .
• C. Rajkuberan, S. Prabukumar, G. Sathishkumar, A. Wilson, K. Ravindran and S. Sivaramakrishnan, J. Saudi Chem. Soc. , 2017, 21 , 911–919  CrossRef   CAS .
• C. Rajkuberan, K. Sudha, G. Sathishkumar and S. Sivaramakrishnan, Spectrochim. Acta, Part A , 2015, 136 , 924–930  CrossRef   CAS .
• A. Lateef, M. A. Azeez, T. B. Asafa, T. A. Yekeen, A. Akinboro, I. C. Oladipo, L. Azeez, S. A. Ojo, E. B. Gueguim-Kana and L. S. Beukes, J. Nanostruct. Chem. , 2016, 6 , 159–169  CrossRef   CAS .
• A. Lateef, M. A. Azeez, T. B. Asafa, T. A. Yekeen, A. Akinboro, I. C. Oladipo, L. Azeez, S. E. Ajibade, S. A. Ojo, E. B. Gueguim-kana and L. S. Beukes, J. Taibah Univ. Sci. , 2015, 10 , 551–562  CrossRef .
• Q. H. Xia, Y. J. Ma and J. W. Wang, Nanomaterials , 2016, 6 , 160  CrossRef .
• F. Huang, Y. Long, Q. Liang, B. Purushotham, M. K. Swamy and Y. Duan, J. Nanomater. , 2019, 2019 , 2418785  Search PubMed .
• C. N. Lok, C. M. Ho, R. Chen, Q. Y. He, W. Y. Yu, H. Sun, P. K. H. Tam, J. F. Chiu and C. M. Che, J. Proteome Res. , 2006, 5 , 916–924  CrossRef   CAS .
• M. Rai, A. Yadav and A. Gade, Biotechnol. Adv. , 2009, 27 , 76–83  CrossRef   CAS .
• L. S. Dorobantu, C. Fallone, A. J. Noble, J. Veinot, G. Ma, G. G. Goss and R. E. Burrell, J. Nanopart. Res. , 2015, 17 , 172  CrossRef .
• F. Kang, P. J. Alvarez and D. Zhu, Environ. Sci. Technol. , 2013, 48 , 316–322  CrossRef .
• H. Xu, F. Qu, H. Xu, W. Lai, Y. A. Wang, Z. P. Aguilar and H. Wei, BioMetals , 2011, 25 , 45–53  CrossRef .
• J. S. Kim, E. Kuk, K. N. Yu, J. H. Kim, S. J. Park, H. J. Lee, S. H. Kim, Y. K. Park, Y. H. Park, C. Y. Hwang, Y. K. Kim, Y. S. Lee, D. H. Jeong and M. H. Cho, Nanomedicine , 2007, 3 , 91–101  Search PubMed .
• J. S. McQuillan, H. Groenaga Infante, E. Stokes and A. M. Shaw, Nanotoxicology , 2011, 6 , 857–866  CrossRef .
• C. M. Zhao and W. X. Wang, Nanotoxicology , 2011, 6 , 361–370  CrossRef .
• W. R. Li, X. B. Xie, Q. S. Shi, H. Y. Zeng, Y. S. Ou-Yang and Y. Ben Chen, Appl. Microbiol. Biotechnol. , 2009, 85 , 1115–1122  CrossRef .
• M. P. Patil and G. Kim, Appl. Microbiol. Biotechnol. , 2017, 101 , 79–92  CrossRef   CAS .
• I. Sondi and B. Salopek-Sondi, J. Colloid Interface Sci. , 2004, 275 , 177–182  CrossRef   CAS .
• J. R. Morones, J. L. Elechiguerra, A. Camacho, K. Holt, J. B. Kouri, J. T. Ramírez and M. J. Yacaman, Nanotechnology , 2005, 16 , 2346–2353  CrossRef   CAS .
• D. Yu and V. W. W. Yam, J. Am. Chem. Soc. , 2004, 126 , 13200–13201  CrossRef   CAS .
• M. G. Bawendi, P. J. Carroll, W. L. Wilson and L. E. Brus, J. Chem. Phys. , 1992, 96 , 946–954  CrossRef   CAS .
• N. Herron, Y. Wang and H. Eckert, J. Am. Chem. Soc. , 1990, 112 , 1322–1326  CrossRef   CAS .
• Z. S. Pillai and P. V. Kamat, J. Phys. Chem. B , 2004, 108 , 945–951  CrossRef   CAS .
• A. Henglein and M. Giersig, J. Phys. Chem. B , 1999, 103 , 9533–9539  CrossRef   CAS .
• J. Y. Song and B. S. Kim, Bioprocess Biosyst. Eng. , 2008, 32 , 79–84  CrossRef .
• M. M. H. Khalil, E. H. Ismail, K. Z. El-Baghdady and D. Mohamed, Arabian J. Chem. , 2014, 7 , 1131–1139  CrossRef   CAS .
• K. Chitra and G. Annadurai, BioMed Res. Int. , 2014, 1–6  Search PubMed .
• S. S. Sana and L. K. Dogiparthi, Mater. Lett. , 2018, 226 , 47–51  CrossRef   CAS .
• A. Khan, U. Farooq, T. Ahmad, R. Sarwar, J. Shafiq, Y. Raza, A. Ahmed, S. Ullah, N. Ur Rehman and A. Al-Harrasi, Int. J. Nanomed. , 2019, 14 , 3983–3993  CrossRef .
• Y. Sun and Y. Xia, Science , 2002, 298 , 5176–5179  Search PubMed .

A study of the physicochemical properties of silver nanoparticles dispersed in various water chemistry settings

• Research paper
• Published: 21 November 2023
• Volume 25 , article number  239 , ( 2023 )

Cite this article

• Jehad.Y. Al-Zou’by   ORCID: orcid.org/0000-0002-0604-8561 1 ,
• La’aly. A. Alsamarraie 1 &
• Kamel. K. Al-Zboon 1  

117 Accesses

Explore all metrics

A Correction to this article was published on 07 February 2024

This article has been updated

The manufacture and application of silver nanoparticles (Ag NPs) will inevitably result in their release and exposure to aquatic systems such as rivers and wastewater. The ultimate purpose of this study is to provide a framework for evaluating and grasping how Ag NPs react when exposed to various water chemistry settings. In addition to pure water, four synthetic media with varied pH, total dissolved solids (TDS), alkalinity (Alk), and chemical oxygen demands (COD) were used; all five media contained an initial 30 mg/l of Ag NPs. These Ag NPs’ absorption intensity, morphology, hydrodynamic diameter (HDD), zeta ( ξ ) potential, and polydespersivity index (PDI) were all measured. Results indicated Ag NPs are guaranteed to be present in all media since a surface plasmon resonance peak (SPR) was maintained at a wavelength of about 430 nm. The findings also demonstrated that, in contrast to other aspects of water chemistry, the media’s pH had the largest bearing on particle behavior, with Ag NPs at pH 2.0 and 12.0 failing to exhibit a distinguishable shape with HDDs of 487.85 nm and 769.6 nm, respectively. TDS produced by sodium chloride (NaCl) and alkalinity appeared to have similar actions. Because of the improved steric stability generated by organic fraction adsorption on the capping of the Ag NPs in the presence of COD, more spherical and closely packed Ag NPs were observed. Overall, the current work provides some fresh insights into the impacts of water chemistry on particle stability, aggregation, distribution, and survival, as well as data on how aggregation and Ag NPs interact and jointly decide particle fate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (Russian Federation)

Instant access to the full article PDF.

Rent this article via DeepDyve

Institutional subscriptions

Similar content being viewed by others

Relationship, importance, and development of analytical techniques: COD, BOD, and, TOC in water—An overview through time

Jazmín Alhelí Aguilar-Torrejón, Patricia Balderas-Hernández, … Teresa Torres-Blancas

Analysis of microplastics in drinking water and other clean water samples with micro-Raman and micro-infrared spectroscopy: minimum requirements and best practice guidelines

Darena Schymanski, Barbara E. Oßmann, … Natalia P. Ivleva

Removal of emerging contaminants from wastewater using advanced treatments. A review

Nadia Morin-Crini, Eric Lichtfouse, … Grégorio Crini

Data availability

The data that support the findings of this investigation are available upon reasonable request from the corresponding author.

Change history

07 february 2024.

A Correction to this paper has been published: https://doi.org/10.1007/s11051-024-05941-4

References  

Gurunathan S, Park JH, Han JW, Kim JH (2015) Comparative assessment of the apoptotic potential of silver nanoparticles synthesized by Bacillus tequilensis and Calocybe indica in MDA-MB-231 human breast cancer cells: targeting p53 for anticancer therapy. Int J Nanomed 10:4203. https://doi.org/10.2147/IJN.S83953

Article   CAS   Google Scholar  

Li WR, Xie XB, Shi QS, Zeng HY, Ou-Yang YS, Chen YB (2010) Antibacterial activity and mechanism of silver nanoparticles on Escherichia coli. Appl Microbiol Biotechnol 85:1115–1122. https://doi.org/10.1007/s00253-009-2159-5

Article   CAS   PubMed   Google Scholar  

Mukherjee P, Ahmad A, Mandal DD, Senapati S, Sainkar SR, Khan MI, Parishcha R, Ajaykumar PV, Alam M, Kumar R, Sastry M (2001) Fungus-mediated synthesis of silver nanoparticles and their immobilization in the mycelial matrix: a novel biological approach to nanoparticle synthesis. Nano Lett 1:515–519. https://doi.org/10.1021/nl0155274

Badawy AME, Luxton TP, Silva RG, Scheckel KG, Suidan MT, Tolaymat TM (2010) Impact of environmental conditions (pH, ionic strength, and electrolyte type) on the surface charge and aggregation of silver nanoparticles suspensions. Environ Sci Technol 44(4):1260–1266. https://doi.org/10.1021/es902240k

Article   ADS   CAS   PubMed   Google Scholar  

Mueller NC, Nowack B (2008) Exposure modeling of engineered nanoparticles in the environment. Environ Sci Technol 42(12):4447–4453. https://doi.org/10.1021/es7029637

Levard C, Hotze EM, Lowry GV, Brown GE Jr (2012) Environmental transformations of silver nanoparticles: impact on stability and toxicity. Environ Sci Technol 46(13):6900–6914. https://doi.org/10.1021/es2037405

Levard C, Hotze EM, Colman BP, Dale AL, Truong L, Yang XY, Bone AJ, Brown GE Jr, Tanguay RL, Di Giulio RT, Bernhardt ES (2013) Sulfidation of silver nanoparticles: natural antidote to their toxicity. Environ Sci Technol 47(23):13440–13448. https://doi.org/10.1021/es403527n

Article   ADS   CAS   PubMed   PubMed Central   Google Scholar  

Auvinen H, Gagnon V, Rousseau DP, Du Laing G (2017) Fate of metallic engineered nanomaterials in constructed wetlands: prospection and future research perspectives. Rev Environ Sci Bio/Technol 16:207–222. https://doi.org/10.1007/s11157-017-9427-0

Article   Google Scholar  

Vale G, Mehennaoui K, Cambier S, Libralato G, Jomini S, Domingos RF (2016) Manufactured nanoparticles in the aquatic environment-biochemical responses on freshwater organisms: a critical overview (doi.org/). Aquat Toxicol 170:162–174. https://doi.org/10.1016/j.aquatox.2015.11.019

Wei L, Lu J, Xu H, Patel A, Chen ZS, Chen G (2015) Silver nanoparticles: synthesis, properties, and therapeutic applications. Drug Discov Today 20(5):595–601. https://doi.org/10.1016/j.drudis.2014.11.014

Feng Y, Deng T, Lai X, Feng Z, Lyu M, Wang S (2020) Effect of properties of silver nanoparticles coated with polar material and the antibacterial activity on marine pathogenic bacteria. J Nanomater 2020:1–11. https://doi.org/10.1155/2020/172830

Yu SJ, Yin YG, Liu JF (2013) Silver nanoparticles in the environment. Env Sci Process Impacts 15:78–92. https://doi.org/10.1039/C2EM30595J . (Search in Google Scholar PubMed)

Jiang J, Wang X, Zhang Y, Zhang J, Gu X, He S, Duan S, Ma J, Wang L, Luo P (2022) The aggregation and dissolution of citrate−coated AgNPs in high ammonia nitrogen wastewater and sludge from UASB−anammox reactor. Int J Environ Res Public Health 19:9502. https://doi.org/10.3390/ijerph19159502

Article   CAS   PubMed   PubMed Central   Google Scholar  

Dorjnamjin D, Ariunaa M, Shim YK (2008) Synthesis of silver nanoparticles using hydroxyl functionalized ionic liquids and their antimicrobial activity. Int J Mol Sci 9:807–820. https://doi.org/10.3390/ijms9050807 . (Search in Google ScholarPubMed PubMed Central)

Eltz FZ, Vebber MC, Aguzzoli C, Machado G, Da Silva Crespo J, Giovanela M (2020) Preparation, characterization and application of polymeric thin films containing silver and copper nanoparticles with bactericidal activity. J Environ Chem Eng 8:1–14 ([Google Scholar] [CrossRef])

Wang R, Zhao P, Yu R, Jiang J, Liang R, Liu G (2022) Cost-efficient collagen fibrous aerogel cross-linked by Fe (III) /silver nanoparticle complexes for simultaneously degrading antibiotics, eliminating antibiotic-resistant bacteria, and adsorbing heavy metal ions from wastewater. Sep Purif Technol 303:122209 ([Google Scholar] [CrossRef])

Najafpoor A, Norouzian-Ostad R, Alidadi H, Rohani-Bastami T, Davoudi M, Barjasteh-Askari F, Zanganeh J (2020) Effect of magnetic nanoparticles and silver-loaded magnetic nanoparticles on advanced wastewater treatment and disinfection. J Mol Liq 303:112640 ([Google Scholar] [CrossRef])

EsmaeiliBidhendi M, Parandi E, MahmoudiMeymand M, Sereshti H, RashidiNodeh H, Joo SW, Vasseghian Y, MahmoudiKhatir N, Rezania S (2023) Removal of lead ions from wastewater using magnesium sulfide nanoparticles caged alginate microbeads. Environ. Res. 216:114416 ([Google Scholar] [CrossRef])

Prosposito P, Burratti L, Venditti I (2020) Silver nanoparticles as colorimetric sensors for water pollutants. Chemosensors 8:26 ([Google Scholar] [CrossRef])

Kodoth AK, Badalamoole V (2020) Silver nanoparticle-embedded pectin-based hydrogel for adsorptive removal of dyes and metal ions. Polym Bull 77:541–564 ([Google Scholar] [CrossRef])

Zhang X, Servos MR, Liu J (2012) Ultrahigh nanoparticle stability against salt, pH, and solvent with retained surface accessibility via depletion stabilization. J Am Chem Soc 134(24):9910–9913. https://doi.org/10.1021/ja303787e

Radziuk D, Skirtach A, Sukhorukov G, Shchukin D, Möhwald H (2007) Stabilization of silver nanoparticles by polyelectrolytes and poly (ethylene glycol). Macromol Rapid Commun 28(7):848–855. https://doi.org/10.1002/marc.200600895

Navarro E, Piccapietra F, Wagner B, Marconi F, Kaegi R, Odzak N, Sigg L, Behra R (2008) Toxicity of silver nanoparticles to Chlamydomonas reinhardtii. Environ Sci Technol 1;42(23):8959–8964. https://doi.org/10.1021/es801785m

Piccapietra F, Allué CG, Sigg L, Behra R (2012) Intracellular silver accumulation in Chlamydomonas reinhardtii upon exposure to carbonate coated silver nanoparticles and silver nitrate. Environ Sci Technol 46(13):7390–7397. https://doi.org/10.1021/es300734m

Keller AA, McFerran S, Lazareva A, Suh S (2013) Global life cycle releases of engineered nanomaterials. J Nanopart Res 15:1–17. https://doi.org/10.1007/s11051-013-1692-4

Maťátková O, Michailidu J, Miškovská A, Kolouchová I, Masák J, Čejková A (2022) Antimicrobial properties and applications of metal nanoparticles biosynthesized by green methods. Biotechnol Adv 58:107905

Article   PubMed   Google Scholar  

Al-zou’by JY, Alzoubi FY, Migdadi AB, Al-Zboon K (2022) Evaluating the impacts of manufactured silver nanoparticles dispersed in various wastewaters on biochemical oxygen demand kinetics of the resulting wastewaters. Nanotechnol Environ Eng 8(1):119–129. https://doi.org/10.1007/s41204-022-00260-2

El Badawy AM, Scheckel KG, Suidan M, Tolaymat T (2012) The impact of stabilization mechanism on the aggregation kinetics of silver nanoparticles. Sci Total Environ 429:325–331. https://doi.org/10.1016/j.scitotenv.2012.03.041

Fernando I, Zhou Y (2019) Impact of pH on the stability, dissolution and aggregation kinetics of silver nanoparticles. Chemosphere 216:297–305. https://doi.org/10.1016/j.chemosphere.2018.10.122

Mwilu SK, El Badawy AM, Bradham K, Nelson C, Thomas D, Scheckel KG, Rogers KR (2013) Changes in silver nanoparticles exposed to human synthetic stomach fluid: effects of particle size and surface chemistry. Sci Total Environ 447:90–98. https://doi.org/10.1016/j.scitotenv.2012.12.036

Chen KL, Elimelech M (2009) Relating colloidal stability of fullerene (C60) nanoparticles to nanoparticle charge and electrokinetic properties. Environ Sci Technol 43(19):7270–7276. https://doi.org/10.1021/es900185p

Li X, Lenhart JJ, Walker HW (2010) Dissolution-accompanied aggregation kinetics of silver nanoparticles. Langmuir 26(22):16690–16698. https://doi.org/10.1021/la101768n

Bhakya S, Muthukrishnan S, Sukumaran M, Muthukumar M, Kumar ST, Rao MV (2015) Catalytic degradation of organic dyes using synthesized silver nanoparticles: a green approach. J Bioremediation Biodegredation 6(5):1. https://doi.org/10.4172/2155-6199.1000313

Lee BG, Griscom SB, Lee JS, Choi HJ, Koh CH, Luoma SN, Fisher NS (2000) Influences of dietary uptake and reactive sulfides on metal bioavailability from aquatic sediments. Science 287(5451):282–284. https://doi.org/10.1126/science.287.5451.282

Li X, Lenhart JJ, Walker HW (2012) Aggregation kinetics and dissolution of coated silver nanoparticles. Langmuir 28(2):1095–1104. https://doi.org/10.1021/la202328n

Sawyer CN, McCarty PL, Parkin GF (2003) Chemistry for environmental engineering and science. McGraw-Hill ( http://repository.vnu.edu.vn/handle/VNU_123/90733 )

Google Scholar  

Zhang H, Oyanedel-Craver V (2012) Evaluation of the disinfectant performance of silver nanoparticles in different water chemistry conditions. J Environ Eng 138(1):58–66. https://doi.org/10.1061/(ASCE)EE.1943-7870.0000460

Alzoubi FY, Al-zou’by JY, Aljarrah IA et al (2021) Physicochemical characteristics of silver nanoparticles: influence of carbonate alkalinity. Nanotechnol Environ Eng 6:68. https://doi.org/10.1007/s41204-021-00162-9

Baird R, Bridgewater L (2017) Standard methods for the examination of water and wastewater. 23rd edition. Washington, D.C., American Public Health Association

Stankus DP, Lohse SE, Hutchison JE, Nason JA (2011) Interactions between natural organic matter and gold nanoparticles stabilized with different organic capping agents. Environ Sci Technol 45(8):3238–3244. https://doi.org/10.1021/es102603p

Furman O, Usenko S, Lau BL (2013) Relative importance of the humic and fulvic fractions of natural organic matter in the aggregation and deposition of silver nanoparticles. Environ Sci Technol 47(3):1349–1356. https://doi.org/10.1021/es303275g

Lynch I, Dawson KA, Lead JR, Valsami-Jones E (2014) Macromolecular coronas and their importance in nanotoxicology and nanoecotoxicology. Front Nanosci 7:127–156. https://doi.org/10.1016/B978-0-08-099408-6.00004-9 . ( Elsevier )

Philippe A, Schaumann GE (2014) Interactions of dissolved organic matter with natural and engineered inorganic colloids: a review. Environ Sci Technol 48(16):8946–8962. https://doi.org/10.1021/es502342r

Lau BL, Hockaday WC, Ikuma K, Furman O, Decho AW (2013) A preliminary assessment of the interactions between the capping agents of silver nanoparticles and environmental organics. Colloids Surf, A 435:22–27. https://doi.org/10.1016/j.colsurfa.2012.11.065

Kwamena NOA, Reid JP, Press CRC (2005) Aerosols. Colloid Sci: Princ, Methods Appl 10:219–244

Zha L, Hu J, Wang C, Fu S, Luo M (2002) The effect of electrolyte on the colloidal properties of poly (N-isopropylacrylamide-co-dimethylaminoethylmethacrylate) microgel latexes. Colloid Polym Sci 280:1116–1121. https://doi.org/10.1007/s00396-002-0734-8

Jiang J, Oberdörster G, Biswas P (2009) Characterization of size, surface charge, and agglomeration state of nanoparticle dispersions for toxicological studies. J Nanopart Res 11:77–89. https://doi.org/10.1007/s11051-008-9446-4

Quintero-Quiroz C, Acevedo N, Zapata-Giraldo J, Botero LE, Quintero J, Zárate-Trivinõ D et al (2019) Optimization of silver nanoparticle synthesis by chemical reduction and evaluation of its antimicrobial and toxic activity. Biomaterials Res 23:27. https://doi.org/10.1186/s40824-019-0173-y

Li Z, Wang Y, Yu Q (2010) Significant parameters in the optimization of synthesis of silver nanoparticles by chemical reduction method. J Mater Eng Perform 19:252–256. https://doi.org/10.1007/s11665-009-9486-7

Alqadi MK, Abo Noqtah OA, Alzoubi FY, Alzouby J, Aljarrah K (2014) pH effect on the aggregation of silver nanoparticles synthesized by chemical reduction. Mater Sci-Pol 32:107–111. https://doi.org/10.2478/s13536-013-0166-9

Article   ADS   CAS   Google Scholar  

Alzoubi FY, Al-zou’by JY, Theban SK, Alqadi MK, Al-khateeb HM, AlSharo ES (2021) Size, stability, and aggregation of citrates-coated silver nanoparticles: contribution of background electrolytes. Nanotechnol Environ Eng 6:1–7. https://doi.org/10.1007/s41204-021-00165-6

Verma SK, Jha E, Panda PK, Thirumurugan A, Patro S, Parashar SKS, Suar M (2018) Molecular insights to alkaline based bio-fabrication of silver nanoparticles for inverse cytotoxicity and enhanced antibacterial activity. Mater Sci Eng, C 92:807–818. https://doi.org/10.1016/j.msec.2018.07.037

Baalousha M (2017) Effect of nanomaterial and media physicochemical properties on nanomaterial aggregation kinetics. NanoImpact 6:55–68. https://doi.org/10.1016/j.impact.2016.10.005

Afshinnia K, Sikder M, Cai B, Baalousha M (2017) Effect of nanomaterial and media physicochemical properties on Ag NM aggregation kinetics. J Colloid Interface Sci 487:192–200. https://doi.org/10.1016/j.jcis.2016.10.037

Mulvaney P (1996) Surface plasmon spectroscopy of nanosized metal particles. Langmuir 12:788–800

Fu LM, Hsu JH, Shih MK, Hsieh CW, Ju WJ, Chen YW, Lee BH, Hou CY (2021) Process optimization of silver nanoparticle synthesis and its application in mercury detection. Micromachines 12:1123

Article   PubMed   PubMed Central   Google Scholar  

Riaz M, Mutreja V, Sareen S et al (2021) Exceptional antibacterial and cytotoxic potency of monodisperse greener AgNPs prepared under optimized pH and temperature. Sci Rep 11:2866. https://doi.org/10.1038/s41598-021-82555-z

Rolim WR et al (2019) Green tea extract mediated biogenic synthesis of silver nanoparticles: characterization, cytotoxicity evaluation and antibacterial activity. Appl Surf Sci 463:66–74

Sartori P, Delamare APL, Machado G, Devine DM, Crespo JS, Giovanela M (2023) Synthesis and characterization of silver nanoparticles for the preparation of chitosan pellets and their application in industrial wastewater disinfection. Water 15:190. https://doi.org/10.3390/w15010190

Singh P, Bodycomb J, Travers B, Tatarkiewicz K, Travers S, Matyas GR, Beck Z (2019) Particle size analyses of polydisperse liposome formulations with a novel multispectral advanced nanoparticle tracking technology. Int J Pharm 566:680–686. https://doi.org/10.1016/j.ijpharm.2019.06.013

Rijckaert H, De Roo J, Van Zele M, Banerjee S, Huhtinen H, Paturi P, Bennewitz J, Billinge SJ, Bäcker M, De Buysser K (2018) Pair distribution function analysis of ZrO2 nanocrystals and insights in the formation of ZrO2-YBa2Cu3O7 nanocomposites. Materials 11:1066. https://doi.org/10.3390/ma11071066

Bhattacharjee S (2016) DLS and zeta potential–what they are and what they are not? J Control Release 235:337–351. https://doi.org/10.1016/j.jconrel.2016.06.017

Feng Y, Deng T, Lai X, Feng Z, Lyu M, Wang S (2020) Effect of properties of silver nanoparticles coated with polar material and the antibacterial activity on marine pathogenic bacteria. J Nanomater 2020:11. https://doi.org/10.1155/2020/1728305

Axson JL, Stark DI, Bondy AL, Capracotta SS, Maynard AD, Philbert MA, Bergin IL, Ault AP (2015) Rapid kinetics of size and pH-dependent dissolution and aggregation of silver nanoparticles in simulated gastric fluid. J Phys Chem C Nanomater Interfaces 119(35):20632–20641. https://doi.org/10.1021/acs.jpcc.5b03634

Chen Q, Cho H, Manthiram K, Yoshida M, Ye X, Alivisatos AP (2015) Interaction potentials of anisotropic nanocrystals from the trajectory sampling of particle motion using in situ liquid phase transmission electron microscopy. ACS Cent Sci 1(1):33–39. https://doi.org/10.1021/acscentsci.5b00001

Zhang F, Allen A, Johnston-Peck A, Liu J, Pettibone J (2019) Transformation of engineered nanomaterials through the prism of silver sulfidation, Nanoscale Advances, [online], https://doi.org/10.1039/C8NA00103K (Accessed June 25, 2023)

Peretyazhko TS, Zhang QB, Colvin VL (2014) Size-controlled dissolution of silver nanoparticles at neutral and acidic pH conditions: kinetics and size changes. Environ Sci Technol 48:11954–11961

Zhou W, Liu Y-L, Stallworth AM, Ye C, Lenhart JJ (2016) Effects of pH, electrolyte, humic acid, and light exposure on the long-term fate of silver nanoparticles. Environ Sci Technol 50:12214–12224

Phanjom P, Ahmed G (2017) Effect of different physicochemical conditions on the synthesis of silver nanoparticles using fungal cell filtrate of Aspergillus oryzae (MTCC No 1846) and their antibacterial effect. Adv Nat Sci Nanosci Nanotechnol 8:10. https://doi.org/10.1088/2043-6254/aa92bc . ([CrossRef] [GoogleScholar])

Mohammed Fayaz A, Balaji K, Kalaichelvan PT, Venkatesan R (2009) Fungal based synthesis of silver nanoparticles-an effect of temperature on the size of particles. Colloids Surf B Biointerfaces 74:123–126. https://doi.org/10.1016/j.colsurfb.2009.07.002 . ([PubMed] [CrossRef] [GoogleScholar])

Levard C, Mitra S, Yang T, Jew AD, Badireddy AR, Lowry GV, Brown GE Jr (2013) Effect of chloride on the dissolution rate of silver nanoparticles and toxicity to E. coli. Environ Sci Technol 47(11):5738–5745. https://doi.org/10.1021/es400396f

Gupta A, Maynes M, Silver S (1998) Effects of halides on plasmidmediated silver resistance in Escherichia coli. Appl Environ Microbiol 64(12):5042–5045

Ho CM, Yau SKW, Lok CN, So MH, Che CM (2010) Oxidative dissolution of silver nanoparticles by biologically relevant oxidants: a kinetic and mechanistic study. Chem Asian J 5(2):285–293

Zhang L, Li X, He R, Wu L, Zhang L, Zeng J (2015) Chloride-induced shape transformation of silver nanoparticles in a water environment. Environ Pollut 204:145–151. https://doi.org/10.1016/j.envpol.2015.04.018

An J, Tang B, Zheng X, Zhou J, Dong F, Xu S et al (2008) Sculpturing effect of chloride ions in shape transformation from triangular to discal silver nanoplates. Deakin University. J Contribution. https://hdl.handle.net/10536/DRO/DU:30095947

Im SH, Lee YT, Wiley B, Xia Y (2005) Large-scale synthesis of silver nanocubes: the role of HCl in promoting cube perfection and monodispersity. Angew Chem Int Ed 44(14):2154–2157. https://doi.org/10.1002/anie.200462208

Cervantes-Avilés P, Huang Y, Keller AA (2019) Multi-technique approach to study the stability of silver nanoparticles at predicted environmental concentrations in wastewater. Water Res 166:115072. https://doi.org/10.1016/j.watres.2019.115072

Naranjo LP, Hernandez HM, Cespedes JH, Echeverry CE (2016) Optic method to determine the organic matter level on water using phthalate potassium. In Latin America Optics and Photonics Conference. OSA. https://doi.org/10.1364/laop.2016.ltu3a.3

Min GK, Bevan MA, Prieve DC, Patterson GD (2002) Light scattering characterization of polystyrene latex with and without adsorbed polymer. Colloids Surf A Physicochem Eng Asp 202:9–21. https://doi.org/10.1016/S0927-7757(01)01060-3

Delay M, Dolt T, Woellhaf A, Sembritzki R, Frimmel FH (2011) Interactions and stability of silver nanoparticles in the aqueous phase: influence of natural organic matter (NOM) and ionic strength. J Chromatogr A 1218:4206–4212. https://doi.org/10.1016/j.chroma.2011.02.074

Gutierrez L, Schmid A, Zaouri N, Garces D, Croue JP (2020) Colloidal stability of capped silver nanoparticles in natural organic matter-containing electrolyte solutions. NanoImpact 19:100242. https://doi.org/10.1016/j.impact.2020.100242

Ali IAM, Ahmed AB, Al-Ahmed HI (2023) Green synthesis and characterization of silver nanoparticles for reducing the damage to sperm parameters in diabetic compared to metformin. Sci Rep 13:2256. https://doi.org/10.1038/s41598-023-29412-3

Download references

Acknowledgements

The authors would like to thank Jordan’s Ministry of Higher Education and Scientific Research’s Scientific Research Support Fund (SRSF) (Project WE/1/6/2021) and Al-Balqa Applied University for their technical assistance and support.

Author information

Authors and affiliations.

Al-Huson University College, Al-Balqa Applied University, Salt, 19117, Jordan

Jehad.Y. Al-Zou’by, La’aly. A. Alsamarraie & Kamel. K. Al-Zboon

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Jehad.Y. Al-Zou’by .

Ethics declarations

Conflict of interest.

The authors declare no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 395 KB)

Rights and permissions.

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Al-Zou’by, J., Alsamarraie, L.A. & Al-Zboon, K.K. A study of the physicochemical properties of silver nanoparticles dispersed in various water chemistry settings. J Nanopart Res 25 , 239 (2023). https://doi.org/10.1007/s11051-023-05895-z

Download citation

Received : 03 April 2023

Accepted : 13 November 2023

Published : 21 November 2023

DOI : https://doi.org/10.1007/s11051-023-05895-z

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Capped silver nanoparticles
• Colloidal stability
• Aggregation
• Dynamic light scattering
• Water chemistry
• Find a journal
• Publish with us
• Track your research

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• My Account Login
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Open access
• Published: 08 February 2023

Green synthesis and characterization of silver nanoparticles for reducing the damage to sperm parameters in diabetic compared to metformin

• Iman A. Mohammed Ali 1 , 2 ,
• Ali Ben Ahmed 1 &
• Hazim Ismail Al-Ahmed 3  

Scientific Reports volume  13 , Article number:  2256 ( 2023 ) Cite this article

6346 Accesses

22 Citations

1 Altmetric

Metrics details

• Biotechnology
• Materials science
• Medical research
• Nanoscience and technology
• Plant sciences

An Author Correction to this article was published on 24 April 2023

This article has been updated

The present study used physics to synthesize silver nanoparticles using aqueous extract of fresh garlic as reducing and as a stabilizing agent silver nitrate solution. This method has proven to be environmentally friendly and safe for the synthesis of stable silver nanoparticles. The acquisition of silver nanoparticles was confirmed by optical detection, that is, by changing the color of the liquid to transparent orange and then blackish brown. Then, the characterization was confirmed using other assays. In this study, it was found that the absorption peak of silver nanoparticles was at a wavelength of 420 nm and the particle size ranged between [50–350] nm. The surface roughness of silver oxide/silver nanoparticles was 9.32 nm with an average square roughness of 21.19 nm, and the energy dispersive spectra showed that the absorption peak was in the region of 3 keV, indicating that the nanoparticles contained crystalline silver. In this study, the stability of the silver nanoparticles was good, as ZP reached (− 19.5). The results confirm that the conductivity increases with the increase in frequency due to the high energy of the photons, which causes the electrons to vibrate in the energy levels and thus increase the energy in the mitochondria and increase the movement of sperm in the Diabetic mice treated with doses of silver nanoparticles. The toxic effect of silver nanoparticles has been evaluated in other studies, in addition to evaluating antioxidants, antifungals, treating cancer cells, regulating cholesterol levels, the effect of these nanoparticles on sex cells in pregnant female mice, heart tension, and many other tests. In this study, the activities and efficacy of silver nanoparticles on sperms were determined in male mice with diabetes caused by STZ, and the treatment period was long (35 days) so that the evaluation period was a complete life cycle of male sex cells and within a long period of time and at an average nano size. This has not been studied in other previous studies. The results indicate that the biosynthesis of silver nanoparticles using garlic plant led to positive results on sperm treatments by contributing to an increase in the number of sperm with reactivation and a decrease in abnormalities in addition to a decrease in mortality due to diabetes. This is evidence that the synthesis of silver nanoparticles using garlic plant size (50–350 nm) can treat impotence and be used in the future in the treatment of many diseases without side effects.

Similar content being viewed by others

Green synthesis, characterization, and biological evaluation of gold and silver nanoparticles using Mentha spicata essential oil

Mir-Hassan Moosavy, Miguel de la Guardia, … Nasser Hajipour

In vitro and in silico studies of silver nanoparticles (AgNPs) from Allium sativum against diabetes

D. Jini, S. Sharmila, … R. M. H. Rajapaksha

Comparative assessment of the biological activity of the green synthesized silver nanoparticles and aqueous leaf extract of Perilla frutescens (L.)

Mansoureh Tavan, Parichehr Hanachi, … Abolfazl Dashtbani-Roozbehani

Introduction

Nanotechnology is described in this study. It is a technique that has attracted a lot of interest in recent years. Nanoparticles represent all types of particles that fall within a diameter of 1–100 nm, and are made of carbon, metal, metal oxides, or organic compounds 1 . When compared with its larger counterpart (Bulk), nanoparticles have distinctive physical, chemical and biological characteristics due to their small size and large surface area, which led to improved interaction or stability during the physical and chemical process, increased mechanical strength and other factors 2 , 3 , 4 . Nanoparticles are distinguished by their different shapes and sizes 5 , in addition to their different diameters. Nanoparticles may be spherical or cylindrical in shape and can be tubular, spiral, flat or irregular in shape and size and range from 1 to 100 nanometers 6 , 7 . Nanotechnology is rapidly developing, and many intensive studies have been conducted to synthesize nanoparticles with distinctive characteristics in terms of cost, speed of completion and the distinctive characteristics of the resulting nanoparticles 8 . NPs have been used in a variety of applications including cooking utensils, renewable energies, agricultural pest control and have been used extensively in the medical field, treating a wide range of diseases, as well as transporting medicines and improving the quality of materials 9 . Silver nanoparticles are among the most important and most common nanoparticles due to the unique properties they possess, such as good conductivity and stability. They are also used in the manufacture of therapeutic alloys, in the treatment of burns and infections resulting from wounds, as anti-cancer cells, and against viruses, bacteria and free radicals 10 , and can be used in the manufacture of tools in contact with food, as a result, it can cause direct contact between silver nanoparticles and workers in this field, and this in turn can cause semi-chronic toxic effects and may interact with the health of the organism, as it was found that AgNPs have the ability to precipitate in The kidneys, testicles, lungs, heart and other organs of the body result in the generation of reactive oxygen species in living cells and can cause immunological or neurotoxicity 11 , on the other hand, many studies have shown that exposure to silver nanoparticles can treat many diseases resulting from External and chronic causes, such as diabetes, pressure, or immune diseases 12 , 13 , 14 . There are few studies that show the effect of silver nanoparticles on sex cells, as many have shown Among the studies, there is a relationship between the amount of the dose once and the approved period in which the infected body is exposed to a quantity of therapeutic nanoparticles again and between the health of the sperm 15 . There are various methods for the synthesis of nanoparticles, including chemical methods, in which highly dangerous compounds are used and toxic for the purpose of minimization and stabilization, causing environmental damage in addition to being expensive and time consuming with high energies. Biological and physical methods are among the ideal methods used for the synthesis of nanoparticles because they are simple, harmless, environmentally friendly, and effective at the same time 16 , 17 . Research and studies have increased to use the biophysical method to manufacture nanoparticles, as it is considered the best to use effective plant-derived compounds such as polyphenols, flavonoids, anthocyanins, ellagic acid and other plant materials that can improve the properties of silver nanoparticles and reduce toxicity resulting from the use of nanoparticles. Metals and salts used in the manufacture of commercial silver nanoparticles 18 .

Our current study focuses on the synthesis of silver nanocomposites derived from biological sources to reduce harmful ions and toxicity resulting from substances that are a source of stabilization and reduction 19 . An aqueous extract of garlic was used 20 , 21 , and testing the toxicity of silver nanoparticles on the sperm of healthy mature mice, and evaluating the role of therapeutic silver nanoparticles in stimulating sperm movement and reducing deformities in sperms as a result of STZ-induced diabetes, and possibly death in some of them and a decrease in the number of sex cells. Treatment with manufactured silver nanoparticles was tested with a long treatment period of up to 35 consecutive days and at a rate of one dose per day, that is, according to the entire life cycle of the sperm, which was not observed in another research. The results indicate that there is no significant toxicity resulting from the silver nanoparticles, and this is considered a success in using a quick and inexpensive method of synthesis, it can be used in the treatment of many diseases and negative effects resulting from diabetes.

Experimental section

Synthesis materials.

Silver nitrate, Streptozotocin obtained from Sigma Corporation, USA industry was used. Fresh garlic was purchased from the traditional medicine store in Baghdad. The garlic plant sample was classified by an expert at the University of Baghdad, College of Science, Department of Biology (AlliumL type/Alliaceae family) 22 . Ethanol was taken from DUKSAN Company The deionized water was used during the preparation of the aqueous extract and all the tools used were washed using distilled water and left to dry using a hot oven before use.

Prepare fresh garlic leaf extract

Fresh garlic was used after washing several times with deionized water (DIW) to remove dust particles, then the plant was left in the air to dry to remove residual moisture. Dry garlic was ground using an ordinary grinder. 15 g of finely ground garlic powder was dispersed in 500 ml DIW, which is of very high purity, using a magnetic stirrer for 30 min at 100 °C. Then, the solution was filtered through filter paper and centrifuged at 4000 rpm for 30 min to remove any impurities and obtain a clear solution. The extract is kept in the refrigerator for later use in the preparation of silver nanoparticles 23 .

Synthesis of silver nanoparticles by green method

The preparation was carried out according to 24 , 25 with some modification. 2 g of silver nitrate was dissolved in 25 ml of distilled water by a 600 RPM magnetic stirrer for 30 min. After that, we add 25 ml of garlic extract gradually with continuous magnetic stirring for an hour at 80 °C. Then a precipitate will form and the color of the solution will turn black. The solution was then left overnight and the precipitate was separated by centrifuge and washed with water and ethanol more than once. The precipitate is dried in an oven at 85 °C for 4 h.

Characterization techniques

X-ray diffraction analysis (xrd).

It is a technique used to study the arrangement of atoms inside crystals, where X-ray diffraction of silver nanoparticles was measured using XRD analysis. The examination was carried out by placing the sample in a centrifuge at 10,000 rpm for 15 min. The precipitate was collected and the resulting silver pellets dried at 50 °C in an oven. The size of silver nanoparticles is calculated using the Scherer equation, which is shown below, \(D = K.\lambda/\beta.{\text{cos}}\theta\) , knowing that the constant k (geometric factor) is equal to \(0.94\) 24 .

Field emission scanning electron microscope (FE-SEM)

The structure of silver nanoparticles and the size and shape of the nanoparticles were studied using scanning electron microscope (EDS-Mapping-Line-EBSD) made in Germany. The examination was carried out after placing the sample in a centrifuge at a rotation speed of 10,000 rpm for 15 min, after which the sample was washed with distilled water and dried at a temperature of 50 degrees Celsius. The sample was placed on a platinum mesh coated with palladium and the sample was analyzed by the radiation passing through the sample and the image was at a dispersion spectrum of (250 INCA Energy) 26 .

Atomic force microscopy (AFM)

Atomic force microscopy was used to examine the surface morphology of silver nanoparticles produced by garlic extract. The examination was carried out after the examined sample was dispersed and placed on a small glass slide under the microscope and at room temperature 27 .

Transmission electron microscopy (TEM)

It is a very powerful technique in materials science that can be described by a beam of high-energy electrons passing through very thin samples. The properties of silver nanoparticles in terms of particle shape and size were studied using TEM technology. An amount of the dried precipitate of nano silver was dissolved in ethanol alcohol, the suspension was placed in the ultrasonic bath for 15 min, then a drop is taken from the suspension and placed on a carbon-coated copper grid. We note that after the sample dries and forms a partially transparent layer, the sample is examined and the resulting image is formed from the shadow of the electron beam falling on the sample 28 .

UV–visible spectra analysis

The UV–visible spectrum of stable silver nanoparticles and aqueous extract of fresh garlic plant was recorded using a UV–Vis spectrometer (Shimadzu-Japanese uv-2450) at 1 nm resolution to ensure the reduction of silver Ag + ions to AgO using garlic extracts as a reducing agent. Samples were scanned in the 300–800 nm range, with a scanning speed of 475 nm/min, at 1 cm optical path and at room temperature. UV–vis absorption spectra were recorded 24 h after incubating the AgNO 3 solution with garlic extract. Distilled water was used as a blank reference for background yellowing from other sources 29 .

Zeta potential measurement

The surface electric charge of Ag NPs was determined by measuring the most stable particles when electrostatic repulsion occurs between the particles. Zeta potential was determined using HAS 300. Zeta sizer based on photon correlation spectroscopy 30 . The analysis time was 60 s, and the average zeta potential was determined. Dispersion was determined as such without dilution.

Dynamic light scattering (DLS)

The hydrodynamic diameter of silver nanoparticles in solution was determined by dynamic light scattering (DLS) and multiple scattering laser diffraction method. Malvern Zeta sizer from Origin/Germany was used 31 .

Biotechnological part

Animals experiment.

Thirty healthy male albino mice weighing about 30 ± 5 g used in the experiment were purchased from Biotechnology Research Center/Al-Nahrain University. All animals were kept in standard conditions of 22 ± 3 °C with a constant 12 h dark and 12 h light exposure cycle, and in a controlled environment at an equilibrium humidity of 50 ± 5%. The animals were left for a week to acclimatize to the experimental conditions while being provided with the standard healthy diet of food and water. The experiment was conducted in the animal house of Al-Nahrain University.

Stimulating experimental diabetes mellitus in albino mice

Diabetes was induced in all male experimental albino mice, except for the healthy control, by giving them a single dose of fresh streptozotocin after being dissolved in saline in an amount \(\left( {200 \;{\text{mg}}/{\text{kg}}} \right)\) of body weight. This dose stimulated diabetes mellitus in male rats, in which hyperglycemia was measured by measuring blood glucose 3–6 days after streptozotocin administration. Using a glucose meter, blood was drawn from the tail vein of mice White mice that showed a blood glucose level higher than 245 mg/dL were taken and with this methodology these animals were selected alone for the current study 32 .

Sperm analysis

The mice were divided into sex groups that were forced to observe the mice. The first group is the negative control group shown, watching these mice. The second group, control diabetic mice, took doses of streptozotocin, the third group was diabetic and treated with metformin (600 mg/kg body weight/day) for 28 days, the fourth group was diabetic and treated with Silver and the fifth was diabetic and treated silver nanoparticles (2 mg/kg body weight/day) 33 . Sperm motility, normal and damaged morphology, and sperm count were examined, and the number was found to be at least 150 sperms from each mouse. Sperm activity and motility analysis was performed by Makler Chamber and using a light microscope (Olympus Corporation, Tokyo, Japan). Where motility was expressed as fast (Grade A) and slow (Grade B) sperm, non-progressive (Grade C) and non-motile (Grade D) sperm. On the other hand, the shapes of sperms were identified by adjusting the optical microscope to magnification × 40 34 .

Ethical declaration

The authors declare that: (1) All methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by ethics committee in Biotechnology research center, at University of Al-Nahrain, Baghdad 35,095 Iraq: Application number 60, Reference number 21-3, date 20 May 2022. (2) All methods are reported in accordance with ARRIVE guidelines for the reporting of animal experiments. (See attached file: “Research Ethics Checklist (Animals)”).

Results and discussion

Xrd analysis.

X-ray diffraction is an important technique for determining crystal structure. It is used to determine the atomic arrangement, lattice parameters, crystal size 35 . Figure  1 shows the pattern of Ag/AgO NPs prepared by the biosynthesis method. There are (8) peaks are shown with different intensities. The diffraction angles at 27.9°, 32.2°, and 54.72° corresponding to planes (100), (111), and (220) respectively, confirm the behavior of AgO Nps and agreement with JCPDS (01–076-1489), while, the diffraction angles at 38.2° and 46.3°, 34.74°, 77.23°, and 81.82° corresponding to planes (111), (200), (220), (311), and (222) respectively. These results illustrated the AgNPs has been prepared, and agreement with the JCPDS (00-001-1167). The crystallite size of Ag/AgO NPs was calculated from the full width half-maximum, Bragg reflections by the Debye–Scherrer equation 36 :

where \(D\) is the crystallite size, \(\lambda = 1.5406\) Å is the wavelength of X-ray, \(\beta\) is the full width half maximum (FWHM) of the peak in radians, and \(\theta\) is the Bragg angle. The crystallite size of Ag/AgO NPs are shown in Table 1 .

XRD pattern of Ag/AgO NPs.

FE-SEM–EDS analysis

The field emission scanning electron microscope (FESESM) provides the ability to study the topography of the surfaces of nanomaterials and determine the possibility of their application in different fields. The morphological images of Ag/AgO NPs created using the biosynthetic process are shown in Fig.  2 a (1 μm) and Fig.  2 b (100 nm). The findings indicate the existence of spherical nanoparticles, which resemble clusters of spherical nanoparticles, with different nano-diameter.

FESEM images of AgNPs at ( a ) 1 µm and ( b ) 300 nm.

AgNPs existence and crystalline structure were study by using EDS analysis. It is widely known that surface Plasmon resonance causes Ag spherical nanoparticles to have a characteristic optical absorption peak about \(3{ }\;{\text{keV}}\) . Figure  3 displayed the absorption peak in the \(3{ }\;{\text{keV}}\) area, demonstrating that NPs were made of crystalline silver.

EDS of Ag/AgO NPs.

The presence of a high content of oxygen may be attributed to the presence of silver oxides in the prepared sample, these results are consistent with the results of XRD analysis. The present results are consistent with the results of the work 37 .

TEM analysis

TEM is one of the advanced analytical measurement tools used for imaging and distinguishing the size and shape of nanoparticles 38 . Figure  4 a,b show the TEM Image of Ag/AgO NPs prepared by the biosynthesis method. The results show that the nanoparticles have a spherical shape and with some aggregation. Figure  4 c explains the histogram size distribution on Ag/AgO NPs with particles size ranging from \(\left[ {50 - 350 } \right] \;{\text{nm}}\) .

TEM Images of ( a , b ) Ag/AgO NPs prepared by biosynthesis method with different magnification, and ( c ) the histogram size distribution.

AFM analysis

The roughness and surface morphology of AgO/AgNPs are indicated in the AFM images, and Fig.  5 . This image was carried out by Naio Nanosurf software, version 3.10.0.28 39 . The results showed that the surface roughness of AgO/AgNPs was \(9.32\;{\text{nm}}\) with an average square roughness of \(21.19\;{\text{nm}}\) , as shown in the Fig.  5 . The present results are consistent with those of the TEM analysis.

AFM images of AgO/AgNPs.

Optical properties

Uv–visible spectra analysis.

Figure  6 a shows the optical absorption spectrum of AgO/AgNPs prepared using garlic extract. The results show that there is an absorption peak at the wavelength \(420\;{\text{nm}}\) that can be attributed to the presence of the surface plasmon resonance (it is the result of the collective movement of free electrons in the silver when light falls on it), which is a characteristic of AgNPs This result is close to the source 40 . The present results are consistent with the results of the work 41 , 42 . Figure  6 b shows the absorption spectrum at a wavelength range (250–800) nm of garlic plant. The peak of the optical absorption spectrum was observed at wavelength 272 nm when using an aqueous garlic plant extract, and this is close to the studies presented in 43 .

UV–visible absorbance spectra of AgO/AgNPs ( a ) extract garlic and ( b ) garlic plant.

Optical absorption coefficient

The attenuation of light intensity as it passes through a substance is described by the absorption coefficient \(\left( \alpha \right)\) . It may be thought of as the total of a material's absorption cross-sections for an optical process per unit volume. The optical absorption coefficient \(\left( \alpha \right)\) can be calculated by the following equation 26 .

where \(A\) is absorbance, \(d\) is thickness and \(ln\left( {10} \right) = 2.30\) .

Figure  7 shows the relation between the optical absorption coefficient \(\left( \alpha \right)\) and the wavelength of AgO/AgNPs prepared by garlic plant extract. The results indicate a peak absorption coefficient at the wavelength of \(420\;{\text{nm}}\) with a high absorption edge close in the ultraviolet region. This curve represents the optical absorption coefficient (α) behavior of AgNPs 44 , 45 .

Variations of absorption coefficient with wavelength of AgO/AgNPs.

Urbach energy

Figure  8 shows the \(Ln\left( \alpha \right)\) versus \(h\nu\) plots obtained for the Ag nanoparticles thin film sample. This plot can be divided into three regions for analysis. The first region belongs to the weak absorption (WAT-Region). It represents the transitions that take place from a tail state located above the valence band to another tail state located below the conduction band, and/or from a tail state located below the conduction band to another tail state located above the valence band. In this WAT region, \(\alpha\) follows \(h\nu\) according to the following relationship 46 :

where \(\alpha_{0}\) is a constant, \(h\nu\) is the photon energy and \(E_{WAT}\) represents the weak absorption tail energy.

Variations of Ln(α) with incident photon energy of AgO/AgNPs.

The Urbach region (U region) (Fig.  8 ) represents the electronic transitions that take place from an extended valence band state to another tail state below the conduction band and/or d from a conduction band state extended to another tail state above the valence band. The \(E_{u}\) can be calculated by the following equation 46 :

where \(\alpha_{0}\) is a constant, \(h\nu\) is the photon energy and \(E_{u}\) is the Urbach energy.

The Urbach energy was calculated by the inverse of slope to the curve. In Fig.  8 we have the Urbach energy \(\left( {E_{u} = 0.25\;{\text{eV}}} \right)\) this low value indicates low density of localized states in the bandgap of Ag nanoparticles thin film. So minimal impurities in our prepared Ag/AgO film.

Optical bandgap analysis

The determination of the optical bandgap \(E_{g}\) was based on this Tauc formula:

After plotting \(\left( {\alpha h\nu } \right)^{2}\) in function of the photon energy \(\left( {h\nu } \right)\) , the bandgap value could be determined using the extrapolating of the linear portion to \(\alpha = 0\) . As can be seen in Fig.  9 , the Tauc plot obtained for the Ag nanoparticles thin film sample. It was obtained from the T region in Fig.  8 as it represents the longest transition. Figure  9 show the relation between the photon energy (eV) and \(\left( {\alpha h\nu } \right)^{2}\) of AgO/AgNPs, by drawing the tangent with the x-axis the direct optical energy gap can be calculated. From the Fig.  9 , the results confirm that the energy gap directly was \(3.39\;{\text{eV}}\) , this meaning the sample needs less energy to stimulate the electrons to move between the energy bands. The current results are in agreement with the results of work 47 .

Tauc plot of AgO/Ag NPs prepared by garlic plant extract.

Refractive index

It has been reported that, the refractive index \(n_{r}\) is a fundamental parameter of optical materials that plays a very important role in optical device designing. Thus, controlling the refractive index of optical nanomaterials makes them convenient for a wide range of applications in industrial and medical applications such as display devices, light-emitting diodes (OLEDs), optical communications, and antibacterial activities. The band gap values can be used to calculate a high frequency refractive index \(n_{r}\) according to the empirical relation applicable to different varieties of compounds:

where \(T_{s}\) is the percent transmittance and A is absorbance.

As can be seen Fig.  10 , the value of the refractive index for the Ag-NPs in the range \(0.113 - 0.116\) . This is close to the usual value of silver \(\left( {0.135} \right)\) 48 . The difference is that our compound is formed by AgO nanoparticles in addition to Ag nanoparticles.

Plot of refractive index as function energy of AgO/Ag NPs.

Optical conductivity

The optical conductivity \(\left( {\sigma_{opt} } \right)\) for this sample was calculated using the absorption coefficient \(\alpha\) , and the refractive index \(n\) data using the following relation 49 :

where \(c\) is the velocity of light in free space, \(\alpha\) is the absorption coefficient and \({ }n_{r}\) is the refractive index.

The optical conductivity of a material determines the relationship between the amplitude of the induced electric field and the density of the induced current in the material for any given frequency. This linear response function is a generalization of electrical conductivity, which is often considered in terms of static electric fields with slow or time-independent differences. It has to do with how conductive a material is, or how much electricity can flow through it. The conductivity of a particular material depends on the frequency of the electric field (that is, how fast it changes) 50 , 51 . Figure  11 shows the photoconductivity as a function of the photon energy (frequency) of silver nanoparticles.

The relation between optical conductivity and energy of AgO/Ag NPs.

The results confirm that the conductivity increases with increasing frequency due to the high energy of the photons, causing the electrons to vibrate in the energy levels.

Figure  12 shows the surface charge measurements of both AgO/AgNPs. The results confirm the dispersion of AgO/AgNPs, which have a zeta potential of − 19.5 (mV) and a mobility of − 1.532 (μmcm/Vs). The present results show a good dispersion state of NPs in liquids 52 . The negative value in this test confirms the occurrence of repulsion between the silver nanoparticles and proves that they are very stable.

Zeta potential values of (A) AgO/AgNPs.

Dynamic light scattering (DLS) analysis

Figure  13 shows the size distribution (by intensity and volume) of AgO/AgNPs prepared by the plant extract. From the figure, the results confirm that the highest peaks of AgO/AgNPs distribution were between 95 and 310 nm. The present results are in close agreement with the results of TEM analysis.

Size Distribution of Ag/AgONPs by ( A ) Intensity and ( B ) Volume. At Temperature 25 °C and Duration 60 s.

Sperms parameters

The results presented in Table 2 and Figs.  14 and 15 indicate that the effect of treatment of Metformin, silver and silver nanoparticles, respectively, on sperm treatments, where the motility and vitality increased significantly \(\left( {P \le 0.05} \right)\) for the group treated with silver nanoparticles when compared to the negative control. While the group treated with silver and Metformin, a significant \(\left( {P \le 0.05} \right)\) increase in movement was observed, but with a less effect. While the abnormalities and the number of deaths were significant as a result of diabetes, where there was a decrease in mortality and Abnormalities in the treated groups.

Sperm without tail & sperm without Head. Slide stained with Nigrosine and Eosin stain (100×).

Dead sperm which take eosin stain and abnormal tail (folded tail sperm). Slide stained with Nigrosine and Eosin stain (100×).

The results showed that the effect of silver nanoparticles on the treatments was positive and significantly increased in motility and living with a significant decrease in deformities and thus mortality in the treated groups. Silver nanoparticles prepared using the environmentally friendly garlic plant protect sperm by increasing the oxidative activity in the immune system, thus preventing reactive oxygen species from lipid peroxidation stimulation responsible for subsequent sperm damage. Our result clearly indicates the important role of silver nanoparticles in various medical applications 53 , 54 .

In this study, silver nanoparticles were successfully generated using a simple, efficient and inexpensive protocol from fresh garlic plant as reducing agent, and silver nanoparticles with a diameter of \(\left[ {50 - 350 } \right] \;{\text{nm}}\) were obtained. They were well crystallized, spherical, stable, and compatible with living cells. This study proved that silver nanoparticles have a great importance and an effective role against diabetes compared to Metformin, and silver nanoparticles succeeded in reducing the high percentage of damage in sperm transactions resulting from diabetes, and thus cause an increase in motility to reach the maximum value with reduced abnormalities.

Data availability

The datasets generated and/or analyzed during the current study are available in the department of biology at university of Baghdad-Iraq: [email protected] (See attached file: “Plant identification certificate). No DNA sequence was performed in this work.

Change history

24 april 2023.

A Correction to this paper has been published: https://doi.org/10.1038/s41598-023-33579-0

Barhoum, A. et al. Review on natural, incidental, bioinspired, and engineered nanomaterials: History, definitions, classifications, synthesis, properties, market, toxicities, risks, and regulations. Nanomaterials 12 , 177 (2022).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Khan, I. et al. Nanoparticles: Properties, applications and toxicities. Arab. J. Chem. 12 , 908–931 (2019).

Article   CAS   Google Scholar  

Baig, N. et al. Nanomaterials: A review of synthesis methods, properties, recent progress, and challenges. Mater. Adv. 2 , 1821–1871 (2021).

Article   Google Scholar  

Sabouri, Z. et al. Plant-based synthesis of NiO nanoparticles using salvia macrosiphon Boiss extract and examination of their water treatment. Rare Met. 39 , 1134–1144 (2020).

Yousaf, S. et al. Nanotechnology and Its Applications: Insight into Bacteriological Interactions and Bacterial Gene Transfer in Nanotechnology for Biomedical Applications (Springer, 2022).

Google Scholar  

Kumari, S. et al. A review on nanoparticles: Structure, classification, synthesis & applications. J. Sci. Res. 65 , 42–46 (2021).

Saif, H. et al. Handbook of Biotechnology (2022).

Singh, S. et al. Point-of-care for evaluating antimicrobial resistance through the adoption of functional materials. Anal. Chem. (2021).

Tulli, F. et al. Synthesis, properties, and uses of silver nanoparticles obtained from leaf extracts. In Green Synthesis of Silver Nanomaterials , Elsevier (2022).

Mazhir, S. N. et al. Dependence of O. Vulgare extract and cold plasma on the formation of silver nanoparticles: Anticancer activity against L20B cells. AIP Conf. Proc. 2213 , 020149 (2020).

Sabouri, Z. et al. Facile green synthesis of Ag-doped ZnO/CaO nanocomposites with Caccinia macranthera seed extract and assessment of their cytotoxicity, antibacterial, and photocatalytic activity. Bioprocess Biosyst. Eng. 45 , 1799–1809 (2022).

Article   CAS   PubMed   Google Scholar  

Malhotra, S. P. K. et al. Biomolecule-Assisted Biogenic Synthesis of Metallic Nanoparticles: Agri-Waste and Microbes for Production of Sustainable Nanomaterials 1st edn. (Elsevier, 2021).

Von White, G. et al. Green synthesis of robust, biocompatible silver nanoparticles using garlic extract. J. Nanomater. 2012 , 1–12 (2012).

El-Refai, A. A. et al. Eco-friendly synthesis of metal nanoparticles using ginger and garlic extracts as biocompatible novel antioxidant and antimicrobial agents. J. Nanostruct. Chem. 8 , 71–81 (2018).

Sabouri, Z. et al. Plant-based synthesis of cerium oxide nanoparticles using Rheum turkestanicum extract and evaluation of their cytotoxicity and photocatalytic properties. Mater. Technol. 37 , 555–568 (2020).

Article   ADS   Google Scholar  

Shreyash, N. et al. Green synthesis of nanoparticles and their biomedical applications: A review. ACS Appl. Nano Mater. 4 , 11428–11457 (2021).

Singh, J. et al. Green synthesis of metals and their oxide nanoparticles: Applications for environmental remediation. J. Nanobiotechnol. 16 , 1–24 (2018).

De, B. et al. Nanobiotechnology–A Green Solution: Biotechnology for Zero Waste: Emerging Waste Management Techniques (Willey, 2022).

Elahi, N. J. et al. Ammonia sensing and cytotoxicity of the biosynthesized silver nanoparticle by arabic gum (AG). Recent Pat. Biotechnol. 13 , 228–238 (2019).

Article   CAS   PubMed   MathSciNet   Google Scholar  

Selvan, D. A. et al. Garlic, green tea and turmeric extracts-mediated green synthesis of silver nanoparticles: Phytochemical, antioxidant and in vitro cytotoxicity studies. J. Photochem. Photobiol., B 180 , 243–252 (2018).

Krishna, S. B. N. Emergent roles of garlic-based nanoparticles for bio-medical applications-a review. Curr. Trends Biotechnol. Pharm. 15 , 349–360 (2021).

CAS   Google Scholar  

University of Baghdad, College of Agriculture. https://www.coagri.uobaghdad.edu.iq

Rahmah, M. I. et al. Preparation of copper oxides/polyvinyl alcohol nanocoating’s with antibacterial activity. Chem. Data Collect. 39 , 100869 (2022).

Amargeetha, A. et al. X-ray diffraction (XRD) and energy dispersive spectroscopy (EDS) analysis of silver nanoparticles synthesized from Erythrina indica flowers. Nanosci. Technol. 5 , 1–5 (2018).

Rath, K. et al. Garlic extract-based preparation of size controlled superparamagnetic hematite nanoparticles and their cytotoxic applications. Indian J. Biotechnol. 18 , 108–118 (2019).

Al-Otibi, F. et al. Biosynthesis of silver nanoparticles using Malva parviflora and their antifungal activity. Saudi J. Biol. Sci. 28 , 2229–2235 (2021).

Gupta, M. Biosynthesized silver nanoparticles using Catharanthus roseus and their antibacterial efficacy in synergy with antibiotics; a future advancement in nanomedicine. Asian J. Pharm. Clin. Res. 14 , 116–124 (2021).

Er, M. Synthesis of Silver Nanoparticles Using a Plasma-Liquid Process (University Sorbonne Paris City, 2019).

Gong, J. et al. Mathematical Modeling of Dye-Sensitized Solar Cells in Dye-Sensitized Solar Cells (Elsevier, 2019).

Kamble, S. et al. Revisiting zeta potential, the key feature of interfacial phenomena, with applications and recent advancements. ChemistrySelect 7 , e202103084 (2022).

Gevorgyan, S. et al. Structural characterization and antibacterial activity of silver nanoparticles synthesized using a low-molecular-weight Royal Jelly extract. Sci. Rep. 12 , 1–12 (2022).

Du Plessis, S. et al. Diabetes Mellitus-Induction: Effect of different Streptozotocin doses on Male Reproductive Parameters: The Possible Ameliorating Effects of Rooibos, Honeybush and Sutherlandia on Diabetes-Induced Reproductive Impairment in Adult Male Wistar. Rats. 120 , 152 (2020).

Alkhalaf, M. I. et al. Green synthesis of silver nanoparticles by Nigella sativa extract alleviates diabetic neuropathy through anti-inflammatory and antioxidant effects. Saudi J. Biol. Sci. 27 , 2410–2419 (2020).

Wang, J. et al. Effects of diabetes mellitus on sperm quality in the db/db mouse model and the role of the FoxO1 pathway. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 27 , e928232–e928241 (2021).

Rashid, T. M. et al. Nano-ZnO decorated on gold nanoparticles as a core-shell via pulse laser ablation in liquid. Optik 248 , 168164 (2021).

Article   ADS   CAS   Google Scholar  

Rahmah, M. I. et al. Preparation of superhydrophobic Ag/Fe2O3/ZnO surfaces with photocatalytic activity. Surf. Eng. 37 , 1320–1327 (2021).

Mehmood, A. et al. Phyto-mediated synthesis of silver nanoparticles from Melia azedarach L. leaf extract: Characterization and antibacterial activity. Arab. J. Chem. 10 , S3048–S3053 (2017).

Shar, A. et al. Facile synthesis and characterization of selenium nanoparticles by the hydrothermal approach. Dig. J. Nanomater. Biostruct. 14 , 867–872 (2019).

Naio Nanosurf software, version 3.10.0.28. https://www.nanosurf.com/en/software/naio

Feng, D. et al. Synthesis of eco-friendly silver nanoparticles using glycyrrhizin and evaluation of their antibacterial ability. Nanomaterials 12 , 2636 (2022).

Goodarzi, V. et al. Evaluation of antioxidant potential and reduction capacity of some plant extracts in silver nanoparticles’ synthesis. Mol. Biol. Res. Commun. 3 , 165 (2014).

PubMed   PubMed Central   Google Scholar  

Balamanikandan, T. et al. Biological Synthesis of silver nanoparticles by using onion (Allium cepa) extract and their antibacterial and antifungal activity. World App. Sci. J. 33 , 939–943 (2015).

Wanyika, H. N. et al. A rapid method based on UV spectrophotometry for quantitative determination of allicin in aqueous garlic extracts. J. Agricult.: Sci. Technol. 12 , 74–82 (2011).

Sosa, I. O. et al. Optical properties of metal nanoparticles with arbitrary shapes. J. Phys. Chem. B 107 , 6269–6275 (2003).

Rasmagin, S. et al. Analysis of the optical properties of silver nanoparticles. Opt. Spectrosc. 128 , 327–330 (2020).

Singh, J. Optical properties of condensed matter and applications. Wiley. 6 , 107–141 (2006).

Das, A. J. et al. Sunlight irradiation induced synthesis of silver nanoparticles using glycolipid bio-surfactant and exploring the antibacterial activity. J. Bioeng. Biomed. Sci. 6 , 1000208 (2016).

The Malvern Reference Manual: Sample dispersion and refractive index guide. How important is the refractive index of nanoparticles - Materials Talks (materials-talks.com).

Abdelghani, Gh. M. et al. Synthesis, characterization, and the influence of energy of irradiation on optical properties of ZnO nanostructures. Sci. Rep. 12 , 20016 (2022).

Article   ADS   CAS   PubMed   PubMed Central   Google Scholar  

Gervais, F. Optical conductivity of oxides. Mater. Sci. Eng. R. Rep. 39 , 29–92 (2002).

Lobo, R. The Optical Conductivity of High-Temperature Superconductors in High-Temperature Superconductors (Elsevier, 2011).

Shnoudeh, A. J. et al. Synthesis, Characterization, and Applications of Metal Nanoparticles in Biomaterials and Bionanotechnology 527–612 (Elsevier, 2019).

Torabian, F. et al. Administration of silver nanoparticles in diabetes mellitus: A systematic review and meta-analysis on animal studies. Biol. Trace Elem. Res. 200 , 1699–1709 (2022).

Nasab, N. K. et al. Green-based synthesis of mixed-phase silver nanoparticles as an effective photocatalyst and investigation of their antibacterial properties. J. Mol. Struct. 1203 , 127411 (2020).

Download references

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and affiliations.

Laboratory of Applied Physic, Faculty of Sciences of Sfax, University of Sfax, 3018, Sfax, Tunisia

Iman A. Mohammed Ali & Ali Ben Ahmed

Ministry of Higher Education & Scientific Research’s, Baghdad, Post Office PO Box 55509, Iraq

Iman A. Mohammed Ali

Biotechnology Research Center, University of Al-Nahrain, Baghdad, 35095, Iraq

Hazim Ismail Al-Ahmed

You can also search for this author in PubMed   Google Scholar

Contributions

Author Agreement Statement We the undersigned declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors (I.A.M.A., A.B.A., H.I.A.-A.) and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We understand that the Corresponding Author “A.B.A.” is the sole contact for the Editorial process. He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. All authors contributed equally to this paper: 1- I.A.M.A.: Methodology, Data curation, conceptualization, writing and reviewing. 2- A.B.A.: Investigation, Data curation, Writing, Reviewing, and editing. 3- H.I.A.-A.: Spectroscopies measurement, Validation, formal analysis. Signed by all authors as follows: First author: I.A.M.A. Seconds and Corresponding Author: A.B.A. Third author: H.I.A.-A.

Corresponding author

Correspondence to Ali Ben Ahmed .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original online version of this Article was revised: The original version of this Article omitted an affiliation for Iman A. Mohammed Ali. The correct affiliations are ‘Laboratory of Applied Physic, Faculty of Sciences of Sfax, University of Sfax, 3018 Sfax, Tunisia.’ and ‘Ministry of Higher Education & Scientific Research’s, Baghdad, Post Office PO Box 55509, Iraq.’

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .

Reprints and permissions

About this article

Cite this article.

Ali, I.A.M., Ahmed, A.B. & Al-Ahmed, H.I. Green synthesis and characterization of silver nanoparticles for reducing the damage to sperm parameters in diabetic compared to metformin. Sci Rep 13 , 2256 (2023). https://doi.org/10.1038/s41598-023-29412-3

Download citation

Received : 21 September 2022

Accepted : 03 February 2023

Published : 08 February 2023

DOI : https://doi.org/10.1038/s41598-023-29412-3

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

Comprehensive antifungal investigation of green synthesized silver nanoformulation against four agriculturally significant fungi and its cytotoxic applications.

• Jyoti Singh
• Ankit Kumar
• Dharmendra Pratap

Scientific Reports (2024)

In situ and bio-green synthesis of silver nanoparticles immobilized on zeolite as a recyclable catalyst for the degradation of OPDs

• Fujiang Zhou
• Hossein Yarahmadi

An integrated approach to occupational health risk assessment of manufacturing nanomaterials using Pythagorean Fuzzy AHP and Fuzzy Inference System

• Samaneh Salari
• Mohsen Sadeghi-Yarandi
• Farideh Golbabaei

Adsorption and photodegradation of organic contaminants by silver nanoparticles: isotherms, kinetics, and computational analysis

• Nnabuk Okon Eddy
• Hillary Abugu

Environmental Monitoring and Assessment (2024)

Eco-conscious photocatalytic degradation of organic textile dyes using green synthesized silver nanoparticles: a safe and green approach toward sustainability

• Jaya Gangwar
• Kadanthottu Sebastian Joseph

Biomass Conversion and Biorefinery (2024)

By submitting a comment you agree to abide by our Terms and Community Guidelines . If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Biosynthesis and assessment of antibacterial and antioxidant activities of silver nanoparticles utilizing Cassia occidentalis L. seed

Affiliations.

• 1 Noida Institute of Engineering and Technology, Greater Noida, India.
• 2 Department of Chemistry, Graphic Era University, Dehradun, India.
• 3 Nanotechnology Centre of Excellence, Addis Ababa Science and Technology University, P.O. Box 16417, Addis Ababa, Ethiopia.
• 4 Department of Environmental Science, Graphic Era University, Dehradun, India.
• 5 Department of Medicinal Plants, Faculty of Agriculture and Natural Resources, Arak University, Arak, 38156-8-8349, Iran. [email protected].
• 6 Institute of Nanoscience and Nanotechnology, Arak University, Arak, 38156-8-8349, Iran. [email protected].
• PMID: 38538702
• PMCID: PMC10973378
• DOI: 10.1038/s41598-024-57823-3

This research explores the eco-friendly synthesis of silver nanoparticles (AgNPs) using Cassia occidentalis L. seed extract. Various analytical techniques, including UV-visible spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDX), were employed for comprehensive characterization. The UV-visible spectra revealed a distinct peak at 425 nm, while the seed extract exhibited peaks at 220 and 248 nm, indicating the presence of polyphenols and phytochemicals. High-resolution TEM unveiled spherical and oval-shaped AgNPs with diameters ranging from 6.44 to 28.50 nm. The SEM exhibiting a spherical shape and a polydisperse nature, thus providing insights into the morphology of the AgNPs. EDX analysis confirmed the presence of silver atoms at 10.01% in the sample. XRD results unequivocally confirm the crystalline nature of the AgNPs suspension, thereby providing valuable insights into their structural characteristics and purity. The antioxidant properties of AgNPs, C. occidentalis seed extract, and butylated hydroxytoluene (BHT) were assessed, revealing IC 50 values of 345, 500, and 434 μg/mL, respectively. Antibacterial evaluation against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli demonstrated heightened sensitivity of bacteria to AgNPs compared to AgNO 3 . Standard antibiotics, tetracycline, and ciprofloxacin, acting as positive controls, exhibited substantial antibacterial efficacy. The green-synthesized AgNPs displayed potent antibacterial activity, suggesting their potential as a viable alternative to conventional antibiotics for combating pathogenic bacterial infections. Furthermore, potential biomedical applications of AgNPs were thoroughly discussed.

Keywords: Antibacterial potential; Antioxidant potential; EDX; Pathogenic bacteria; SEM; Silver nanoparticles; TEM; XRD.

© 2024. The Author(s).

• Anti-Bacterial Agents / chemistry
• Antioxidants / chemistry
• Antioxidants / pharmacology
• Bacillus subtilis
• Escherichia coli
• Metal Nanoparticles* / chemistry
• Plant Extracts / chemistry
• Plant Extracts / pharmacology
• Senna Plant*
• Silver / chemistry
• Silver / pharmacology
• Spectrometry, X-Ray Emission
• Spectroscopy, Fourier Transform Infrared
• X-Ray Diffraction
• Antioxidants
• Plant Extracts
• Anti-Bacterial Agents

• Architecture and Design
• Asian and Pacific Studies
• Business and Economics
• Classical and Ancient Near Eastern Studies
• Computer Sciences
• Cultural Studies
• Engineering
• General Interest
• Geosciences
• Industrial Chemistry
• Islamic and Middle Eastern Studies
• Jewish Studies
• Library and Information Science, Book Studies
• Life Sciences
• Linguistics and Semiotics
• Literary Studies
• Materials Sciences
• Mathematics
• Social Sciences
• Sports and Recreation
• Theology and Religion
• Publish your article
• The role of authors
• Promoting your article
• Abstracting & indexing
• Publishing Ethics
• Why publish with De Gruyter
• How to publish with De Gruyter
• Our book series
• Our subject areas
• Your digital product at De Gruyter
• Contribute to our reference works
• Product information
• Tools & resources
• Product Information
• Promotional Materials
• Orders and Inquiries
• FAQ for Library Suppliers and Book Sellers
• Repository Policy
• Free access policy
• Open Access agreements
• Database portals
• For Authors
• Customer service
• People + Culture
• Journal Management
• How to join us
• Working at De Gruyter
• Mission & Vision
• De Gruyter Foundation
• De Gruyter Ebound
• Our Responsibility
• Partner publishers

Your purchase has been completed. Your documents are now available to view.

Silver nanoparticles: synthesis, characterisation and biomedical applications

Nanotechnology is a rapidly growing field due to its unique functionality and a wide range of applications. Nanomedicine explores the possibilities of applying the knowledge and tools of nanotechnology for the prevention, treatment, diagnosis and control of disease. In this regard, silver nanoparticles with diameters ranging from 1 to 100 nm are considered most important due to their unique properties, ability to form diverse nanostructures, their extraordinary range of bactericidal and anticancer properties, wound healing and other therapeutic abilities and their cost-effectiveness in production. The current paper reviews various types of physical, chemical and biological methods used in the production of silver nanoparticles. It also describes approaches employing silver nanoparticles as antimicrobial and antibiofilm agents, as antitumour agents, in dentistry and dental implants, as promoters of bone healing, in cardiovascular implants and as promoters of wound healing. The paper also explores the mechanism of action, synthesis methods and morphological characterisation of silver nanoparticles to examine their role in medical treatments and disease management.

1 Introduction

Considering the epitome of scientific discoveries and inventions ever since the advent of man on Earth, the emergence of nanotechnology is a relatively recent development. However, the last 30 years have been witness to the invention of nanotechnology in the 1980s and its rise to prominence during the early 2000s with wide commercial applications in various sectors. Materials with unique properties are downsized to the level of individual atoms and molecules, collectively called nanoparticles, generally ranging from 1 to 100 nm. Potential uses for these particles include commercial, industrial, agricultural and medicinal applications. Although nanoparticles have an identical chemical composition to the parent material, physical properties including colour, strength, magnetic and thermodynamic properties and other physical aspects may differ widely. The application of nanomaterials in medicine is also a recent venture with most applications still in the research and development stage.

However, certain materials, due to their exemplary medicinal properties, have been part of the medicinal domain since time immemorial. Silver (Ag), due to its extraordinary range of bactericidal properties and therapeutic abilities, has been a part of medical treatment and management of various diseases since ancient times. It is a well-recognised fact that silver ions and silver-based compounds have a great microbial killing capacity [ 1 , 2 ]. However, the development of technologies and a better understanding of the mechanism of silver in disease prevention via killing of microorganisms have opened the door towards their uses in nanomedicine. Many approaches and methods have evolved for the effective synthesis of silver nanoparticles, including physical, chemical and biological techniques. While physical and chemical methods are commercially more cost-effective, the biological methods are relatively less harsh on the environment [ 3 ].

In nanomedicine, silver nanoparticles are extremely important due to their attractive physicochemical properties and biological functionality, including their high antimicrobial efficiency and relatively non-toxic, wide spectrum of bactericidal properties [ 4 ], anticancer properties and other therapeutic abilities, their unique ability to form diverse nanostructures [ 5 ] and their relatively low manufacturing cost [ 6 ].

Silver nanoparticles are intensively explored nanostructures ranging between 1 and 100 nm, primarily used for unconventional and enhanced biomedical applications in such areas as drug delivery, wound dressings, tissue scaffolding and protective coating applications. Moreover, the impressive available surface of nanosilver allows the coordination of many ligands, thus enabling tremendous possibilities with respect to the surface functionalisation of silver nanoparticles. Silver is routinely used in the form of silver nitrate (NO 3 − ) for antimicrobial activity. In addition, silver nanoparticles are more beneficial as compared to free silver because their greater surface area increases the exposure of microbes. Furthermore, silver nanoparticles have emerged as a great field of interest for researchers because of their unique activity against a large range of microorganisms and due to resistance against commonly used antibiotics [ 7 ]. To date, several studies have reported applications in fields such as food processing, agriculture and agro-based industries, biomedical and medical remediation, healthcare products, consumer products, numerous industries, pharmaceuticals, in diagnostics, orthopaedics, drug delivery, imaging, filters as antitumour agents and as enhancer of tumour-killing effects of anticancer drugs.

The current review summarises the important approaches for the synthesis of silver nanoparticles as well as their various roles as antimicrobial and antibiofilm agents, antitumour agents, in dentistry, bone healing, dental implants, cardiovascular implants and wound healing.

2 Synthesis/production of silver nanoparticles

Several procedures are employed for the manufacture of silver nanoparticles, including physical, chemical and biological syntheses. It is worth noting that each method has its own advantages and disadvantages. During biological synthesis of silver nanoparticles, the organism acts as a capping agent, reducing agent or stabilising agent and reduces Ag + to produce Ag 0 [ 8 ]. Due to their low cost, high yields and low toxicity on the human body and the environment, biological methods based on natural products obtained from microorganism and plant sources have increased in popularity in recent years [ 9 ]. Different methods for synthesis of silver nanoparticles are described in the following sections.

2.1 Chemical methods

Various methods are available to synthesise silver nanoparticles. Chemical methods are beneficial because the equipment required is more convenient and simple than that used in biological methods. It has already been reported that silver ions receive electrons from the reducing agent and become converted into the metallic form, which finally aggregates to form silver nanoparticles. Among the silver salts used in chemical synthesis of silver nanoparticles, AgNO 3 is one of the most commonly used due to properties such as low cost ( Table 1 ) [ 10 , 11 ]. In 2002, Sun and Xia reported the synthesis of monodispersed silver nanocubes through reducing nitrate [ 12 ]. Mukherji and Agnihotri synthesised silver nanoparticles using AgNO 3 as a precursor, and sodium borohydride and trisodium citrate as stabilising agents. It has been reported that sodium borohydride is a good reducing agent for the synthesis of silver nanoparticles having a size range of 5–20 nm. In comparison, trisodium citrate is the most effective reducing agent for the synthesis of silver nanoparticles of the size range 60–100 nm [ 13 ]. Polyvinylpyrrolidone (PVP) as a size controller and a capping agent, with ethylene glycol as a solvent and a reducing agent, is reported to give rise to silver nanoparticles with an average size less than 10 nm [ 14 ]. Patil et al. confirmed the synthesis of silver nanoparticles using hydrazine hydrate as the reducing agent and polyvinyl alcohol as the stabilising agent. Their results revealed that the resultant nanoparticles had a spherical morphology and these particles showed significant applications in biotechnology and biomedical science [ 15 ]. According to another important study, the synthesised silver nanoparticles were found to be spherical with different sizes [ 16 ].

The AgNO 3 solution is heated to the reaction temperature in the precursor heating method and the nanoparticle size is observed to be most affected by the ramping rate, whereas in the precursor injection method, a silver nitrate aqueous solution is injected, and the reaction temperature is a key factor for the reduction of particle size and for achieving monodispersity [ 17 ]. High yield is the main advantage of chemical methods, compared to physical methods. Chemical methods are highly expensive, and chemicals and compounds used for silver nanoparticle synthesis such as borohydride, 2-mercaptoethanol, citrate and thio-glycerol are hazardous and toxic. It is extremely difficult to produce silver nanoparticles with a definite size and it requires an additional step to prevent particle aggregation [ 18 ]. Numerous hazardous and toxic by-products are produced during synthesis. Moreover, the reducing agents used in these methods are toxic [ 19 ].

2.2 Physical methods

Physical methods for the preparation of silver nanoparticles include evaporation–condensation and laser ablation. The main drawbacks of these methods are the huge amount of energy required, plus long duration for completion of the whole process.

Lee and Kang have reported that thermal decomposition of Ag + –oleate complexes results in the synthesis of monodispersed silver nanocrystallites [ 20 ]. In a study conducted by Jung et al., a small ceramic heater was used to prepare metal nanoparticles through evaporation/condensation processes. It was noticed that a constant temperature of the heater surface with time generated polydispersed nanoparticles. These silver nanoparticles were spherical and non-agglomerated [ 21 ]. Recently, it has been demonstrated that the polyol process produces spherical nanoparticles with different sizes under laser ablation [ 17 , 22 ]. To examine the effects of laser wavelength on the particle size, silver nanoparticles were synthesised through ablation with different lasers and it was noticed that decrease in laser wavelength reduced the average diameter of particles from 29 to 12 nm [ 23 ]. Nanosized particles of silver were prepared by Tsuji et al. through laser ablation in water to compare the formation efficacy and the size of colloidal particles produced by femtosecond pulses with colloidal particles produced by nanosecond laser pulses. The formation efficiency for femtosecond pulses was significantly lower than that for nanosecond pulses. Besides this, the size of colloids prepared via femtosecond pulses was less dispersed than that of colloids prepared by nanosecond laser pulses [ 24 ]. Seigal and colleagues examined the synthesis of silver nanoparticles through a direct physical deposition of metal into the glycerol. This approach was found to be a good alternative for time-consuming chemical processes. Furthermore, consequential nanoparticles were resistant to aggregation and had a narrow size distribution [ 25 ]. Speed, no requirement for toxic reagents and radiation utilised as a reducing agent are the advantages of physical methods of production. Solvent contamination, minimal yield, non-uniform distribution and high energy consumption are the disadvantages of physical methods ( Table 2 ) [ 26 ].

Chemical methods for the synthesis of monodispersed and quasi-spherical silver nanoparticles [ 11 ]

2.3 Biological methods

Production of silver nanoparticles by physical and chemical processes is expensive, time consuming and eco-unfriendly. Hence, it is very important to develop an environmentally and economically friendly method, which does not involve toxic chemicals [ 32 ] and avoids the other problems associated with chemical and physical means of production. Biological methods fill these gaps and have various applications in health management through regulation of various biological activities. Biological production methods include the use of fungi, bacteria and yeasts as well as plant sources. These sources make this approach very popular for medical applications of nanoparticles.

It has been reported that nanoparticle production methods based on microorganisms and plants are safe, economic and are relatively less harmful to the environment than chemical synthesis [ 33 , 34 ]. Moreover, microorganisms and plants are able to absorb and accumulate inorganic metallic ions from their surrounding environment [ 35 ]. Biological production of silver nanoparticles mainly involves the use of microorganisms and plant sources ( Figure 1 ) [ 36 ].

Different biological methods for the synthesis of silver nanoparticles.

Physical and chemical syntheses of silver nanoparticles

Abbreviations: UV-Vis – ultraviolet-visible spectroscopy, FIFFF – flow field-flow fractionation, DSC – differential scanning calorimetry, TEM – transmission electron microscopy, EDS – energy-dispersive spectroscopy, EFTEM – energy filtered TEM, FTI R – Fourier transform infrared, DLS – dynamic light scattering, XRD – X-ray diffraction, TGA – thermogravimetric analysis.

2.3.1 Production in bacteria

Recently, a study was performed to produce silver nanoparticles through the reduction of aqueous Ag + ions using the culture supernatants of various bacteria. This approach was demonstrated to be fast and the interaction of silver ions with the cell filtrate generated silver nanoparticles within 5 min. Moreover, this study also reported that piperitone partially inhibited the reduction of Ag + to metallic silver nanoparticles [ 37 ]. It is important to note that the nitro reduction activity of Enterobacteriaceae is inhibited by the natural product piperitone. It is assumed that the bioreduction of silver ions to silver nanoparticles might be partially inhibited by different strains of Enterobacteriaceae such as Klebsiella pneumoniae . Korbekandi and colleagues studied the optimisation of silver nanoparticle production by Lactobacillus casei subspecies casei , confirming the bioreductive synthesis of silver nanoparticles [ 38 ]. Liu et al. showed the formation of nanoparticles from dried cells of Bacillus megaterium [ 39 ]. Das et al. have described the extracellular synthesis of silver nanoparticles through a bacterial strain. The study showed that the treatment of Bacillus strain CS 11 with AgNO 3 resulted in the formation of silver nanoparticles extracellularly [ 40 ].

2.3.2 Synthesis/production based on fungi

Various types of fungi have been reported to be involved in the production of silver nanoparticles [ 41 ]. The production of silver nanoparticles by fungi has been found to be very quick. Many researchers have studied the biosynthesis of silver nanoparticles by fungi in detail [ 32 ]. One study has shown the extracellular biosynthesis of spherical silver nanoparticles by interaction of Fusarium solani with silver nitrate [ 42 ]. Syed and colleagues have reported the biosynthesis of silver nanoparticles by the Humicola sp. It was shown that a precursor solution was reduced by the interaction between Humicola sp. and Ag + ions and extracellular nanoparticles were produced [ 43 ]. Owaid and colleagues have reported the production of silver nanoparticles by the bioreduction of silver nitrate induced by the extract of Pleurotus cornucopiae [ 44 ]. Xue et al. conducted an experiment to biosynthesise silver nanoparticles with antifungal properties using Arthroderma fulvum [ 45 ]. Vigneshwaran et al. reported that the interaction of silver nitrate solution with the fungus Aspergillus flavus resulted in the accumulation of silver nanoparticles on the surface of its cell wall [ 46 ]. Furthermore, Bhainsa and D’Souza had investigated the extracellular biosynthesis of silver nanoparticles using Aspergillus fumigatus . The results indicated that the interaction of silver ions with the cell filtrate generated silver nanoparticles in a very short time [ 47 ]. However, using Fusarium oxysporum results in an extracellular production of silver nanoparticles with a size of 5–50 nm [ 48 ]. Additionally, incubation of Phanerochaete chrysosporium mycelium with silver nitrate solution produced silver nanoparticles [ 49 ]. Korbekandi and colleagues showed the bioreductive production of silver nanoparticles by using Fusarium oxysporum [ 50 ].

2.3.3 Production in algae

This approach is a feasible substitute for physical and chemical methods of nanoparticle production because it is economic and eco-friendly [ 51 ]. Furthermore, algae have a high capacity for metal uptake. It has been seen that biological sources such as marine algae have the capacity to catalyse specific reactions. This capacity is key to modern and realistic biosynthetic plans [ 52 ]. A study based on the algae extract has shown that the change of colour from yellow to brown can indicate the reduction of silver ions to silver nanoparticles. In addition, Rajeshkumar and colleagues noticed the deep brown colour of silver nanoparticles at 32 h and it was observed that the time of incubation was directly associated with the increase in colour intensity [ 53 ]. Silver nanoparticles were synthesised through the reduction of aqueous solutions of silver nitrate with powder and solvent extracts of Padina pavonia . Additionally, the achieved nanoparticles showed high stability, fast formation and small size [ 54 ]. Salari and colleagues reported the production of silver nanoparticles through bioreduction of silver ions induced by Spirogyra varians [ 55 ].

2.3.4 Production in yeast

Yeasts have been reported to have the capability to produce silver nanoparticles. In addition, silver nanoparticle production methods based on yeast are cost-effective as well as eco-friendly. In this regard, Niknejad and colleagues performed a study that was based on Saccharomyces cerevisiae . It was noted that with increasing time of incubation, the colourless sample slowly turned to reddish-brown after adding Ag + ions to the yeast culture. Furthermore, the colour of the solution changed into strong reddish-brown [ 56 ]. In 2003, Kowshik et al. have reported the extracellular synthesis of nanoparticles through the interaction of soluble silver with a silver-tolerant yeast in its log phase of growth [ 57 ].

2.3.5 Synthesis based on plants/plant extracts

Like other biological methods, production in plants is better than chemical and physical methods because high temperature, energy and toxic chemicals are not needed and it is cost-effective and environment-friendly [ 58 ]. Numerous active constituents are present in Aloe vera leaves. These ingredients include lignin, hemicellulose and pectins, which have been shown to have a clear role in the reduction of silver ions [ 59 ]. In a recent study, silver nanoparticles were synthesised using an aqueous solution of the plant extract of Saudi Arabia Origanum vulgare L. The result demonstrated that synthesis of silver nanoparticles occurred by reduction of Ag + ions. During this process, the colour of the reaction mixture was converted from light brown to dark brown. On the other hand, in the absence of plant extract no change in colour was observed under the same conditions [ 60 ]. The results of another study reported that the colour of the aqueous silver nitrate solution was changed from faint light to yellowish brown after the addition of different concentrations of aqueous leaf extracts of Azadirachta indica [ 61 ]. López-Miranda et al. biosynthesised silver nanoparticles rapidly by using Tamarix gallica plant extract [ 62 ].

Chinnappan et al. have reported a fast and simple method for the synthesis of silver nanoparticles using an extract of Bauhinia purpurea flower [ 63 ]. In 2016, Ibraheim et al. reported the synthesis of silver nanoparticles from silver nitrate using aqueous pomegranate juice extract as a reducing agent and their results demonstrated that the use of juice extract leads to a quick synthesis of silver nanoparticles from AgNO 3 solution. It was found that the colour changed from light yellow to reddish-brown with the formation of silver nanoparticles after exposure to microwaves for a few minutes [ 64 ]. Lakshmanan et al. synthesised silver nanoparticles using Cleome viscosa plant extract and the study revealed that extract of this plant has a good ability to reduce silver nitrate into metallic silver [ 65 ].

Prasad et al. employed aqueous leaf extracts of Moringa oleifera to develop a simple and quick method for bioreduction of silver nanoparticles. Their findings concluded that Moringa oleifera had a strong potential for synthesis of silver nanoparticles via rapid reduction of silver ions [ 66 ]. In this regard, another finding indicated a fast and convenient method for the synthesis of silver nanoparticles using Ficus benghalensis leaf extract and the reduction of silver ions into silver nanoparticles occurred within short periods (5 min) of reaction time without using any hard conditions [ 67 ]. Moreover, the treatment of aqueous solutions of silver nitrate and chloroauric acid with neem leaf extract leads to the fast synthesis of stable silver and gold nanoparticles at high concentrations [ 68 ]. Earlier investigators are accountable for pioneering nanoparticle synthesis through using plant extracts [ 60 , 68 , 69 , 70 , 71 , 72 ].

Ponarulselvam et al. concluded that extracts of the leaves of Catharanthus roseus could be used in the synthesis of silver nanoparticles that exhibited antiplasmodial activity against Plasmodium falciparum [ 73 ]. Some studies have reported that silver ions are reduced extracellularly in the presence of fungi to generate stable silver nanoparticles in water [ 42 , 74 ]. Zarghar and colleagues have indicated the formation of spherical silver nanoparticles by using methanolic leaf extracts of Vitex negundo and demonstrated the antibacterial activity of these silver nanoparticles against both Gram-positive and Gram-negative bacteria [ 75 ].

2.3.6 Synthesis based on DNA

DNA can be used as a reducing agent for silver nanoparticle synthesis. High affinity of silver ions with DNA base pairs makes DNA a template stabiliser. Synthesised silver nanoparticles were found at N-7 phosphate and guanine base pair on DNA strand. Another study reported the synthesis of silver nanoparticles with calf thymus DNA [ 36 , 76 ].

3 Characterisation techniques for nanoparticles

Characterisation is an important step in the green synthesis of nanoparticles. It is a pivotal step to determine the morphology, surface chemistry, surface area and disparity in the nature of any silver nanoparticle. Various techniques are used for characterisation of silver nanoparticles ( Figure 2 ).

Various techniques used for characterisation of silver nanoparticles.

3.1 UV-Vis spectrophotometry

This technique is most widely utilised to characterise metallic nanoparticles by monitoring their stability and synthesis [ 77 ]. The synthesis of a metallic nanoparticle from its particular salt provides a characteristic peak with strong absorptions in the visible region [ 78 ]. Various studies have revealed that, in general, the absorption band at around 200–800 nm wavelength is best for the characterisation of particles in the size range of 2–100 nm [ 79 ]. The valence and conduction bands in silver nanoparticles are very close to each other. Electrons move freely in these bands and give rise to a surface plasmon resonance absorption band. The silver nanoparticle’s absorption depends upon the chemical surroundings, dielectric medium and particle size. Examination and study of the surface plasmon peak is well known for several metal nanoparticles having a size range of 2–100 nm. Stability of silver nanoparticles produced through biological methods was examined for about 12 months and a surface plasmon resonance peak at the same wavelength was found using UV-Vis spectrophotometry [ 18 ].

3.2 X-ray diffraction analysis (XRD)

XRD is an analytical technique broadly used to observe the structure of crystalline metallic nanoparticles by penetration of X-rays deeply into the material [ 80 , 81 ]. The resulting diffraction pattern confirms the formation of nanoparticles with crystalline structure [ 82 ].

To calculate the particle size from the XRD data, the Debye–Scherrer equation is applied by determining the width of the Bragg reflection law according to the equation: d = Kλ / β cos θ , where d is the particle size (nm), K is the Scherrer constant, λ is the wavelength of X-ray, β is the full width half maximum and θ is the diffraction angle (half of Bragg angle) that corresponds to the lattice plane [ 83 ].

Therefore, the structural features of various materials, such as biomolecules, polymers, glasses and superconductors, can be examined by XRD [ 18 ]. Moreover, XRD is a potent method for the study of nanomaterials [ 84 ].

3.3 Fourier transform infrared spectroscopy (FTIR)

FTIR can be utilised to explore the surface chemistry of synthesised metal nanoparticle and to observe the involvement of biomolecules in nanoparticle synthesis [ 80 ] and can be used for analysing different capping agents.

In FTIR, infrared rays are passed through the sample, some are absorbed by the sample and the remaining pass through it. The resulting spectra indicate the absorption and transmission that are characteristic of the sample material [ 85 ]. FTIR is a cost-effective, appropriate, simple and non-invasive technique to determine the function of biological molecules in the reduction of silver nitrate to silver [ 18 ].

3.4 Energy-dispersive X-ray spectroscopy (EDX)

EDX is an important technique for the analysis of the elemental composition of a sample and its application to nanotechnology has been documented. All elements have different atomic structures producing a unique set of peaks in the X-ray spectrum [ 86 ] and these can be used to study the elemental composition of any nanoparticle.

3.5 Scanning electron microscopy (SEM)

The topography and morphology of nanoparticles can be observed by SEM, which is also used to calculate the size of various nanoparticles at the micro- (10 −6 ) and nano (10 −9 ) scales [ 87 , 88 ]. A high-energy electron beam, produced by SEM, is directed at the surface of the sample nanoparticles and the backscattered electrons produced give the characteristic features of the sample [ 89 ]. Electron microscopy analysis is used to examine the changes in the morphology of the cell before and after nanoparticle treatment. Several studies have reported that the visible modifications in cell shape and perforations of nanoparticles in the cell wall have been used as indicators of the antimicrobial action of nanoparticles [ 90 , 91 ]. Using SEM, control bacterial cells exhibited smooth and undamaged structures, while cells treated with silver nanoparticles for 60 min were significantly damaged, with clear morphological changes to the cell membrane leading to loss of membrane integrity [ 92 ].

3.6 Transmission electron microscopy (TEM)

TEM is a very useful technique for characterisation of nanoparticles, which provides information on size and morphology of nanoparticles [ 80 , 93 ]. TEM has a 1,000-fold higher resolution compared with SEM [ 94 ] and its images give more exact information related to size, shape and crystallography of the nanoparticles [ 81 ].

3.7 Dynamic light scattering (DLS)

DLS is a well-recognised technique for measuring the size and size distribution of molecules. It has been used to measure the size of nanoparticles and it is commonly used to characterise nanoparticles. Moreover, DLS has been extensively employed for sizing magnetic nanoparticles in the liquid phase [ 95 , 96 ] and its role in characterisation of various types of nanoparticles has been documented. The size of nanoparticle determined by DLS is generally larger than TEM due to the effect of Brownian motion. This technique can be used to determine the average size of nanoparticles in liquids [ 18 ].

3.8 Auger electron spectroscopy (AES)

AES is a surface‐sensitive analytical technique that derives from the interaction of an electron beam and atoms in residence at the surface of a sample [ 97 ] and is an outstanding analytical method for nanotechnology [ 98 ]. The oxidation state of silver as a component of a hybrid substance can be probed by AES [ 99 ].

3.9 Low-energy ion scattering (LEIS)

LEIS is a commonly used surface analytical technique, which is well recognised for its supreme surface sensitivity. With the help of this technique, the structure and the elemental composition of a given sample can be deduced [ 100 – 102 ]. Moreover, high sensitivity LEIS is a valuable surface analytical method for the characterization of SAM-functionalised nanomaterials [ 103 ].

4 Factors influencing the synthesis of silver nanoparticles

methods of production

temperature

shape and size.

4.1 Methods for the production of silver nanoparticles

There are many methods to manufacture nanoparticles, including physical and chemical techniques and biological protocols. Various organic or inorganic chemicals as well as living organisms are used for the synthesis of nanoparticles in these methods [ 104 ]. It has already been discussed that green synthesis is preferable to other methods because it is eco-friendly and cost-effective. Furthermore, green synthesis does not use high temperature, energy and toxic chemicals [ 58 ].

4.2 Temperature

Temperature has been found to be an important factor for the production of nanoparticles. Spherical nanoparticles are synthesised in the presence of elevated temperature. In contrast, nanotriangle formation occurs mostly at lower temperatures [ 90 ]. It has been shown that increase in temperature between 30 and 90°C boosts the frequency of synthesis [ 89 , 105 ] and sometimes also encourages the formation of smaller silver nanoparticles [ 106 ]. There are multiple reports suggesting that 25–37°C (room temperature) is the optimal range for the biogenic synthesis of metal nanoparticles.

Most studies suggest that nanoparticle stability is improved in basic media than acidic [ 107 , 108 ]. However, a very high pH (pH > 11) was found to have some drawbacks such as the formation of agglomerated and unstable silver nanoparticles [ 109 ]. Therefore, it can be concluded that the shape and size of nanoparticles are determined by the pH.

Decreasing the reaction time (minutes–hours) is another factor affecting the reduction of ions to a bulk metal with variant shapes. The optimum time period results in higher concentrations of nanoparticles in the medium, indicated by high absorbance peaks. Rai and colleagues have suggested that shape, size and optical properties of anisotropic nanoparticles can be fine-tuned by varying temperature. It was determined by employment of varying growth conditions and formation of different sizes of nanoparticles such as spherical, triangular, hexagonal and rectangular [ 70 ].

4.5 Shape and size

The shape and size of nanoparticles are crucial in determining their properties. It has been concluded that optimal activities are determined by the shape and size of the nanoparticle and most properties of nanoparticles are size-dependent [ 110 ].

5 Applications of silver nanoparticles in various industries

Silver nanoparticles have many properties making them desirable materials for a variety of industries, such as antibacterial and optical properties, availability and low production, processing and storage costs [ 111 ]. Furthermore, silver nanoparticles with a diameter of about 100 nm are very important for large-scale industries due to their small particle size, high surface area, quantum confinement and spread without agglomeration [ 112 ]. For these reasons, silver nanoparticles are used as alternatives in the manufacture of widely used goods and industries. Nowadays, silver nanoparticles are being explored in various industries such as medicine, biotechnology, material science and energy sectors, and particularly medicinal goods (wound dressings, medication delivery, biosensors and medical diagnostics, orthopaedics), the food and textile industries and water disinfection systems [ 113 ]. Furthermore, silver nanoparticles are often used for commercial products such as cosmetics and food processing as an essential additive. Furthermore, nanoparticles have many important uses, including spectrally sensitive solar energy absorption coatings and intercalation content for electrical batteries, optical receptors, polarising filters, chemical reaction catalysts, biolabelling and as antimicrobial agents [ 114 ]. In the agricultural sector, the utilisation of nanoparticles contributes to addressing the food security challenges raised by climate change. In the field of medicine [ 115 ], silver nanoparticles have introduced a new dimension to wound dressing and artificial implants and to the prevention of post-operative microbial contamination [ 116 ]. Silver nanoparticles are highly relevant as antibacterial agents in the textile, health and food industries. As an antibacterial agent, silver nanoparticles have various applications such as in the treatment of water, home appliances and sterilising medical equipment. Furthermore, silver nanoparticles are used in several textile goods ( Table 3 ) [ 112 ]. The utilisation of preservatives can also be decreased due to the utilisation of silver nanoparticles [ 117 ].

Use of silver nanoparticles in different industries

5.1 Uses of silver nanoparticles in biomedical sciences

Silver nanoparticles play an important role in the modulation of various activities such as antimicrobial, antibiofilm, antiparasitic, antifouling, anticancer, antiviral and drug-delivery systems. Applications of silver nanoparticles are presented in Figure 3 .

Applications of silver nanoparticles.

5.1.1 Antiviral activity

Nanoparticles provide an alternative to drugs for treating and controlling the growth of viral pathogens. Biosynthesis of silver nanoparticles could result in potent antiviral agents to restrict virus functions. Suriyakalaa et al. studied bio-silver nanoparticles with convincing anti-HIV actions at an early stage of the reverse transcription mechanism [ 118 ]. Biosynthesised metallic nanoparticles have multiple binding sites for gp120 of the viral membrane to control the function of the virus. While another study reported that bio-based nanoparticles act as effective virucidal agents against free HIV or cell-associated virus [ 119 ]. Silver nanoparticles have been demonstrated to exert antiviral activity against HIV-1 at non-cytotoxic concentrations. These silver nanoparticles were evaluated to elucidate their mode of antiviral action against HIV-1 using a panel of different in vitro assays [ 120 ]. Another study reported the antiviral activity of silver nanoparticles with or without a polysaccharide coating against monkeypox virus. This study found that silver nanoparticles meaningfully inhibit monkeypox virus infection in vitro [ 121 ].

Exposing Tacaribe virus to silver nanoparticles prior to infection facilitated virus uptake into the host cells, whereas it was noticed that silver-treated virus showed significant reduction in viral RNA production and this finding demonstrated that silver nanoparticles are capable of inhibiting arenavirus infection in vitro [ 122 ]. Another study result showed that among the three types of silver nanoparticle-MHCs tested, Ag30-MHCs displayed the highest efficacy for viral inactivation [ 123 ].

5.1.2 Antifungal activity

Silver nanoparticles have been shown to possess antifungal activity towards different fungi [ 124 , 125 ], but the mechanism behind it has not been fully understood. Silver nanoparticles have a tendency to disturb the structure of the cell membrane. This damaging effect on the membrane integrity and inhibition of the budding process has been suggested as the mechanism for antifungal activity of silver nanoparticles against Candida albicans species [ 126 ]. In a study of antibacterial and antifungal activity, nano-Ag sepiolite fibres containing monodispersed silver nanoparticles were used as the source of silver. Low melting soda lime glass powder containing nanoparticles had a good antibacterial and antifungal activity [ 127 ]. A study demonstrated that fluconazole in combination with silver nanoparticles showed the highest inhibition against Candida albicans . In this study, Alternaria alternata fungus was used for the extracellular biosynthesis of silver nanoparticles [ 128 ]. It was established that the concentration of silver nanoparticles between 30 and 200 mg/L significantly decreased the growth of fungi [ 129 ]. Furthermore, cell culture supernatant of strain GP-23 was used to synthesise silver nanoparticles and the biosynthesised silver nanoparticles showed a powerful antifungal activity [ 130 ]. Trichoderma harzianum cell filtrate was applied in the production of silver nanoparticles which resulted in their production within 3 h and TEM analysis demonstrated ellipsoid and spherical nanoparticles having a size range of 19–63 nm and an average size of 34.77 nm [ 131 ].

Jalal et al. concluded by the TEM analysis that the treatment of Candida cells with silver nanoparticles resulted in an extreme deformation of cells. Furthermore, the cell contraction was enhanced due to the interaction of nanoparticles with the fungal cell wall and membrane. It resulted in the disturbance of the structure of the cell membrane and inhibited the normal budding process due to the destruction and loss of membrane integrity [ 132 ]. Jalal et al. further showed the antimicrobial effects of Syzygium cumini -derived silver nanoparticles against Candida species and concluded that these nanoparticles have the capability to suppress the multiplication, germ tube and biofilm formation as well as secretion of hydrolytic enzymes by Candida species [ 133 ].

5.1.3 Antiparasitic action

Silver nanoparticles have been found to possess larvicidal activities against the dengue vectors Aedes aegypti [ 134 ] and Culex quinquefasciatus [ 135 ]. Allahverdiyev et al. conducted a study to evaluate the effects of silver nanoparticles on biological parameters of Leishmania tropica . This study confirmed that silver nanoparticles possess antileishmanial effects due to their potential to inhibit the proliferation activity of promastigotes. Furthermore, silver nanoparticles were found to inhibit the survival of amastigotes in host cells, and this effect was increased in the presence of UV light [ 136 ]. Saad and colleagues synthesised silver and copper nanoparticles and tested their antiparasitic activity, finding that silver nanoparticles significantly reduced the oocyst viability of Cryptosporidium parvum . These findings suggest that silver nanoparticles were very effective and safe against parasitic infections of Entamoeba histolytica and Cryptosporidium parvum [ 137 ].

5.1.4 Antibacterial activity

Silver nanoparticles play an important role as antibacterial agents. Silver nanoformulations have also been found to possess a good capability for inhibiting the growth of microorganisms such as bacteria ( Figure 4 ) [ 138 ]. Silver nanoparticle-based devices are commonly used in dental and cardiovascular implants because they do not cause infections. It has been reported that silver nanoparticles have a powerful antibacterial activity against both Gram-negative and Gram-positive bacteria [ 139 , 140 ]. Some studies have reported that Gram-negative bacteria are more sensitive than Gram-positive bacteria to silver nanoparticles [ 140 , 141 ], whereas contradictory results were observed by other researchers [ 142 ]. They suggested that the differential sensitivity of both bacterial species could be attributed to the difference in their structural characteristics as well as the shape and size of silver nanoparticles.

Diagram of antibacterial activity mechanisms of silver nanoparticles.

Furthermore, it was reported that the antibacterial activities of various types of antibiotics were increased in the presence of silver nanoparticles [ 37 ]. The antimicrobial activities of silver nanoparticles against different pathogenic organisms were investigated by Nanda and Saravanan. The maximum antimicrobial activity was observed against methicillin-resistant Staphylococcus aureus [ 143 ]. Antibacterial and antibiofilm activities of silver nanoparticles alone and in combination with conventional antibiotics against various human pathogenic bacteria were examined. The findings of the study confirmed that in combination with antibiotics, there were noteworthy antimicrobial and antibiofilm effects which were seen at the lowest concentration of silver nanoparticles that were biosynthesised by using a plant extract of Allophylus cobbe [ 144 ]. Morones et al. indicated that size was an important factor affecting the bactericidal properties of silver nanoparticles [ 145 ].

Qasim and colleagues examined the antimicrobial activities of silver nanoparticles encapsulated in poly- N -isopropylacrylamide-based polymeric nanoparticles. The study revealed that the bacteriostatic activities of polymeric nanoparticles were determined by the size of nanoparticle as well as the amount of AgNO 3 [ 146 ]. A pioneering study has discussed the antibacterial activity mechanism of silver nanoparticles [ 147 ].

5.1.5 Antifouling action

It is known that biofouling is one of the major challenges faced by the water industry and public health. Silver nanoparticles of Rhizopus oryzae fungal species have been tested on contaminated water. Silver nanoparticles derived using Lactobacillus fermentum cells were found to control biofilm formation and were confirmed to have antifouling properties [ 91 ]. Moreover, silver nanoparticles are also applied to several types of environmental concerns such as air disinfection, water disinfection and surface disinfection [ 148 ]. A recent study demonstrated that an efficient management of biofouling can be achieved by a direct deposition of silver nanoparticle coatings on environmentally friendly surfaces [ 149 ].

5.1.6 Antibiofilm activity

Worldwide, the food industry and community are subject to microbial biofilm challenges. Johani and colleagues conducted a study to evaluate decontaminated endoscope channels for residual bacterial contamination and biofilm presence. They demonstrated that 47% of channels were culture positive, with α-haemolytic streptococci from gastroscopes and coliforms from colonoscopes the most frequently isolated species. However, all 39 channels examined contained biofilm. Besides, it was observed that environmental bacteria were the chief components of this biofilm but potent pathogens were also present through all samples [ 150 ]. Due to the rapid emergence of antimicrobial resistance and the limited effect of antibiotics on bacterial biofilm, alternative strategies such as green silver nanotechnology are gaining attention due to the unique size, shape and structure of nanoparticles produced by this method.

Recently, people have started using silver nanoparticles for inhibiting biofilm formation, but the exact mechanism of the inhibitory action of silver nanoparticles is not clearly understood. Chen et al. categorised antibiofilm strategies into two groups: (i) treatments that inhibit the biofilm formation specifically and (ii) prevention and use of modified biomaterials in biomedical devices to make them resistant to biofilm formation [ 151 ]. Previous reports supported the new approaches for modification of the surface of biomedical devices to prevent microbial attachment, adhesion and growth [ 152 ]. In a study of the antibiofilm activity of silver nanoparticles against multidrug-resistant Gram-negative bacterial isolates, they effectively restricted biofilm formation [ 153 ]. Based on their findings, Martinez-Gutierrez et al. concluded that the formation of biofilms was prevented by silver nanoparticles and bacteria were killed in recognised biofilms [ 154 ].

Palanisamy et al. conducted a study to check the effect of silver nanoparticles on the formation of biofilm. They demonstrated that the formation of biofilms in resistant strains was inhibited by silver nanoparticles [ 155 ]. Another recent study was made to evaluate the contacts of silver nanoparticles with Pseudomonas putida biofilms. It was shown that treatment with silver nanoparticles suppressed the biofilms [ 156 ]. Kalishwaralal et al. investigated the antibiofilm activity of silver nanoparticles against biofilms formed by Pseudomonas aeruginosa and Staphylococcus epidermidis . The treatment of these organisms with silver nanoparticles showed inhibition of biofilm formation [ 157 ]. Mohanty and colleagues performed a study to check the antibacterial activity of silver nanoparticles against a panel of human pathogens. The data supported the previous studies that the biofilm formation was disturbed by silver nanoparticles. Furthermore, antibacterial activity was found to be improved, compared to a human cationic antimicrobial peptide [ 158 ].

5.2 Pharmacological uses of silver nanoparticles

5.2.1 wound healing.

The biochemical events in wound repair are categorised into stages including inflammatory reaction, cell proliferation and synthesis of the elements that form the extracellular matrix and remodelling [ 159 ]. Silver nanoparticles either alone or in combination with antibacterial medicines are commonly used to promote wound healing without infection. Silver nanoparticle-based dressings have been applied to a fibroblast cell culture in vitro and to partial thickness burns in patients. A study has shown that silver nanoparticle-based dressings do not exert an influence on the proliferation of fibroblasts and keratinocytes that lead to a reestablishment of normal skin [ 160 ]. Besides, a combination of silver nanoparticles along with antibiotics such as tetracycline works more effectively than silver nanoparticles or tetracycline treatment alone against a bacterial load while wound macroscopic contraction was increased. Additionally, these findings suggest the use of a combination of silver nanoparticles and antibacterial medicines in the therapy of infected skin wounds [ 161 ].

Mats of gelatine fibres containing silver nanoparticles were prepared to form a wound-dressing pad by Rujitanaroj et al. [ 162 ]. A further study compared the efficacy of two antimicrobial agents including nanocrystalline silver and cadexomer iodine. In this study, community nursing clients with leg ulcers compromised by bacterial burden were chosen for a randomised-controlled trial. Their wounds were treated with either silver or iodine dressings. The results confirmed that treatment by using silver compounds was faster with a quick healing rate [ 163 ].

5.3 The use of silver nanoparticles in the food industry

Small quantities of silver nanoparticles are effective antimicrobials against bacteria and viruses but harmless to humans. This makes them useful for food sanitisation. Silver nanoparticles are used in widely available fresh food bags such as Sunriver Industrial Co. nanosilver food bags [ 114 , 118 ].

6 Other therapeutic uses

6.1 antitumour activity.

Cancers are multifactorial diseases, including alteration in cell signalling pathways. Natural products or active compounds of medicinal plants have a proven role in cancer prevention through killing of cancer cells. In this regard, silver nanoparticles are found to have an important role in cancer cell inhibition and thereby, inhibition of development and progression of the disease. It has been confirmed that silver and gold nanoparticles have a vital role in the inhibition of the growth of cancer cells. Studies based on lymphoma cell lines were performed to investigate the potential of silver nanoparticles as an antitumour agent in vitro and in vivo . The study confirmed the dose-dependent cytotoxicity of silver nanoparticles against lymphoma cells in vitro and also indicated a role in the induction of apoptosis. Additionally, it was reported that nanoparticles significantly increased the survival time in the tumour mouse model and also had a role in the decrease of the volume of ascitic fluid in tumour-bearing mice [ 164 ].

The effect of silver nanoparticles on gene expression in the human lung epithelial cell line was analysed. The study revealed that exposure to silver nanoparticles influenced the cell cycle and directed to an arrest in the G2/M phase [ 165 ]. It has recently been reported that silver nanoparticles induced autophagy in cancer cells through activating the PtdIns3K signalling pathway. Moreover, wortmannin, an inhibitor of autophagy, significantly enhanced the antitumour effect of silver nanoparticles in a melanoma cell model [ 166 ] and green synthesised silver nanoparticles showed a dose-dependent response based on the human lung cancer study [ 167 ].

The cytotoxic and oxidative effects of silver nanoparticles synthesised from Panax ginseng leaves were examined in human cancer cell lines. The study demonstrated that the nanoformulation had anticancer activity [ 168 ]. Khateef and colleagues examined the cytotoxicity of silver nanoparticles at various concentrations. It was noticed that the inhibition of cell growth was enhanced with increasing concentrations of the silver nanoparticles. Moreover, the increase in the concentration of silver nanoparticles led to decreased cell viability [ 169 ].

6.2 Drug-delivery systems

Drug delivery refers to methods of transporting natural or pharmaceutical compounds in order to attain a desired potential therapeutic effect. Various formulations based on nanoparticles have been reported to play an important role in drug targeting against various diseases. Polymers, such as microspheres and nanoparticles prepared from biodegradable compounds, have been reported to be used in drug targeting against disease processes such as inflammation and for cancer chemotherapy [ 170 ]. Hybrid molecular units holding silver nanoparticles are used to design drug-delivery systems to target inflammatory and infectious diseases [ 171 , 172 ]. Benyettou et al. synthesised a silver nanoparticle-based drug-delivery system to attain a simultaneous intracellular delivery of drugs such as doxorubicin and alendronate. This drug-delivery system has been shown to increase the anticancer therapeutic indices of both drugs [ 173 ]. Another study demonstrated that the hybridisation of Fe 3 O 4 and silver nanoparticles can be used as high performance magnetic hyperthermia mediators [ 174 ].

6.3 Role in dentistry

Silver nanoparticles have been determined to have potential applications in dentistry through their ability to kill microbes or inhibit their growth. Moreover, the role of silver nanoparticles in areas including endodontics [ 155 , 156 ] and dental prostheses [ 175 ] has been noted. The potential use of silver oxide nanoparticles synthesised using Ficus benghalensis root extract has been reported and examined for its antibacterial activity against dental bacterial strains. The study demonstrated that a blend of the extract and Ag 2 O silver nanoparticles had powerful antibacterial activities [ 176 ]. Pérez-Díaz et al. reported that silver nanoparticles inhibited the growth of a planktonic Streptococcus mutans clinical isolate and killed Streptococcus mutans biofilms [ 177 ]. Santos et al. determined the bactericidal activity of silver nanoparticles against Streptococcus mutans . Thus, silver nanoparticles are suggested to have an effective role in the prevention of dental caries [ 178 ].

6.4 Orthopaedic implant/bone healing

In orthopaedic implants, silver nanoparticle-based devices are now preferred because of a lower risk of infection. Silver nanoparticle-coated stainless steel is used in order to reduce infections associated with orthopaedic implants. Structural characterisation of a unique hydroxyapatite (HAp) combined with silver nanoparticles has been examined for its application in orthopaedic implants and it was confirmed that it is well suited to orthopaedic implantation [ 179 ]. Another study has reported that silver nanoparticle-doped HAp scaffolds, showing a unique antibacterial activity, are able to prevent bacterial infections linked with bone implants [ 180 ]. In an experimental study, Ciobanu and colleagues obtained a novel HAp-based material with high biocompatibility. They demonstrated that viability was improved, and the activation of murine macrophages was potentiated by nanocrystalline silver-doped HAp [ 181 ].

6.5 Cardiovascular implants

Silver nanoparticle-based devices have proven applications in cardiovascular implants because of their antibacterial and anticoagulant activity. A recent study was performed to examine perfusion pressure and left ventricle pressure as physiological characteristics of cardiovascular function in response to silver nanoparticles. This study determined that hypertension strengthened the cardiotoxicity of silver nanoparticles [ 182 ]. Multilayer films containing nanosilver particles have been reported to function as antibacterial and anticoagulant agents. These multilayer films may have a good potential for surface modification of medical devices, particularly for cardiovascular implants [ 10 ].

7 Toxicity of silver nanoparticles

The use of silver nanoparticles is rapidly increasing worldwide in many sectors, including health. However, it is essential to minimise the risk of the adverse effect of silver nanoparticles on both human patients and the environment. In this regard, several studies based on animal models have been conducted to evaluate the toxicity of silver nanoparticles and their effect on physiology and tissue architecture. Ag + leads to a non-classical permeability increase in the mitochondrial inner membrane. Moreover, in rat liver mitochondria, there was an increased permeability that caused mitochondrial swelling, abnormal metabolism and ultimately cellular apoptosis [ 183 ]. A further study found significant depletion of glutathione, decreased mitochondrial membrane potential and enhanced reactive oxygen species levels. These results suggest that in liver cells the cytotoxicity of Ag particles in the size range 15–100 nm is probably facilitated via oxidative stress [ 184 ].

A study was carried out to examine the suitability of a mouse spermatogonial stem cell line as a model to assess nanotoxicity and established a concentration-dependent toxicity for all types of particles tested, and silver nanoparticles were the most toxic in this regard [ 185 ]. In 2010, Laban et al. showed that both dissolved and particulate forms of silver caused toxicity to fish embryos [ 186 ]. Sung et al. have indicated that a prolonged exposure to silver nanoparticles induced changes in lung function as well as decreases in tidal volume and other inflammatory responses [ 187 ]. In a study on female mice exposed to various sizes of silver nanoparticles (10, 60 and 100 nm), the smaller silver nanoparticles (10 nm) showed the highest level of histopathological changes of congestion, single cell necrosis and focal necrosis in the liver and congestion in the spleen, suggesting that the smaller-sized particles showed higher acute toxicity in mice [ 188 ].

8 Conclusion

Silver nanoparticles play a significant role in health management due to their wide range of applications as antimicrobial agents, antitumour agents and in food packing, in agriculture and in the healthcare sector. Furthermore, it is well known that most of the empirical use of antibiotics exhibits resistance leading to ineffectiveness. Hence, biofilm forming bacteria present a serious problem. To overcome this problem of antibiotic resistance, there is increased worldwide attention on alternative treatment strategies. These alternative strategies include potential use of silver nanoparticles and surface coating or impregnation of nanomaterials as antibiofilm agents. In addition, silver nanoparticles are the most studied and utilised nanoparticles in the management of various diseases including cancer, wound healing, dental implants and other therapeutics such as modulating biological activities. With enhanced understanding and improved technology, the application of these novel particles in medicine will establish a standard platform for the prevention and treatment of multidrug resistance and biofilm pathogens.

Acknowledgments

The author acknowledges the Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Saudi Arabia for providing the facilities for this study.

Conflict of interest: The authors state no conflict of interest.

Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

[1] Slawson RM, Trevors JT, Lee H. Silver accumulation and resistance in Pseudomonas stutzeri. Arch Microbiol. 1992;158:398–404. 10.1007/BF00276299 . Search in Google Scholar

[2] Zhao G, Stevens SE. Multiple parameters for the comprehensive evaluation of the susceptibility of Escherichia coli to the silver ion. BioMetals. 1998;11:27–32. 10.1023/a:1009253223055 . Search in Google Scholar

[3] Hulkoti NI, Taranath TC. Influence of physico-chemical parameters on the fabrication of silver nanoparticles using Petrea volubilis L. stem broth and its anti-microbial efficacy. Int J Pharm Sci Drug Res. 2017;9:72–8. 10.25004/IJPSDR.2017.090206 . Search in Google Scholar

[4] Durán N, Durán M, de Jesus MB, Seabra AB, Fávaro WJ, Nakazato G. Silver nanoparticles: a new view on mechanistic aspects on antimicrobial activity. Nanomed Nanotechnol Biol Med. 2016;12:789–99. 10.1016/j.nano.2015.11.016 . Search in Google Scholar PubMed

[5] Sohn EK, Johari SA, Kim TG, Kim JK, Kim E, Lee JH, et al. Aquatic toxicity comparison of silver nanoparticles and silver nanowires. BioMed Res Int. 2015;2015:893049. 10.1155/2015/893049 . Search in Google Scholar PubMed PubMed Central

[6] Capek I. Preparation of metal nanoparticles in water-in-oil (w/o) microemulsions. Adv Colloid Interface Sci. 2004;110:49–74. 10.1016/j.cis.2004.02.003 . Search in Google Scholar PubMed

[7] Hutchison JE, Greener. Nanoscience: a proactive approach to advancing applications and reducing implications of nanotechnology. ACS Nano. 2008;2:395–402. 10.1021/nn800131j . Search in Google Scholar PubMed

[8] Zewde B, Ambaye A, Stubbs Iii J, Raghavan D. A review of stabilized silver nanoparticles–synthesis, biological properties, characterization, and potential areas of applications. Nanomedicine. 2016;4(1043):1–4. Search in Google Scholar

[9] Shanmuganathan R, Karuppusamy I, Saravanan M, Muthukumar H, Ponnuchamy K, Ramkumar VS, et al. Synthesis of silver nanoparticles and their biomedical applications – a comprehensive review. Curr Pharm Des. 2019;25:2650–60. 10.2174/1381612825666190708185506 . Search in Google Scholar PubMed

[10] Ge L, Li Q, Wang M, Ouyang J, Li X, Xing MM. Nanosilver particles in medical applications: synthesis, performance, and toxicity. Int J Nanomed. 2014;9:2399–407. 10.2147/IJN.S55015 . Search in Google Scholar PubMed PubMed Central

[11] Calderón-Jiménez B, Johnson ME, Montoro Bustos AR, Murphy KE, Winchester MR, Vega Baudrit JR. Silver nanoparticles: technological advances, societal impacts, and metrological challenges. Front Chem. 2017;5:6. 10.3389/fchem.2017.00006 . Search in Google Scholar PubMed PubMed Central

[12] Sun Y, Xia Y. Shape-controlled synthesis of gold and silver nanoparticles. Science. 2002;298:2176–9. 10.1126/science.1077229 . Search in Google Scholar PubMed

[13] Agnihotri S, Mukherji S. Size-controlled silver nanoparticles synthesized over the range 5–100 nm using the same protocol and their antibacterial efficacy. RSC Adv. 2013;4:3974–83. 10.1039/C3RA44507K . Search in Google Scholar

[14] Dang TMD, Le TTT, Fribourg-Blanc E, Dang MC. Influence of surfactant on the preparation of silver nanoparticles by polyol method. Adv Nat Sci Nanosci Nanotechnol. 2012;3:035004. 10.1088/2043-6262/3/3/035004 . Search in Google Scholar

[15] Patil RS, Kokate MR, Jambhale CL, Pawar SM, Han SH, Kolekar SS. One-pot synthesis of PVA-capped silver nanoparticles their characterization and biomedical application. Adv Nat Sci Nanosci Nanotechnol. 2012;3:015013. 10.1088/2043-6262/3/1/015013 . Search in Google Scholar

[16] Amirjani A, Firouzi F, Haghshenas DF. Predicting the size of silver nanoparticles from their optical properties. Plasmonics. 2020;15:1077–82. 10.1007/s11468-020-01121-x . Search in Google Scholar

[17] Kim D, Jeong S, Moon J. Synthesis of silver nanoparticles using the polyol process and the influence of precursor injection. Nanotechnology. 2006;17:4019–24. 10.1088/0957-4484/17/16/004 . Search in Google Scholar PubMed

[18] Zhang X-F, Liu Z-G, Shen W, Gurunathan S. Silver nanoparticles: synthesis, characterization, properties, applications, and therapeutic approaches. Int J Mol Sci. 2016;17:1534. 10.3390/ijms17091534 . Search in Google Scholar PubMed PubMed Central

[19] Ganaie SU, Abbasi T, Abbasi SA. Green synthesis of silver nanoparticles using an otherwise worthless weed mimosa (Mimosa pudica): feasibility and process development toward shape/size control. Part Sci Technol. 2015;33:638–44. 10.1080/02726351.2015.1016644 . Search in Google Scholar

[20] Lee DK, Kang YS. Synthesis of silver nanocrystallites by a new thermal decomposition method and their characterization. ETRI J. 2004;26:252–6. 10.4218/etrij.04.0103.0061 . Search in Google Scholar

[21] Jung JH, Cheol OhH, Soo Noh H, Ji JH, Kim SS. Metal nanoparticle generation using a small ceramic heater with a local heating area. J Aerosol Sci. 2006;37:1662–70. 10.1016/j.jaerosci.2006.09.002 . Search in Google Scholar

[22] Torras M, Roig A. From silver plates to spherical nanoparticles: snapshots of microwave-assisted polyol synthesis. ACS Omega. 2020;5:5731–8. 10.1021/acsomega.9b03748 . Search in Google Scholar

[23] Tsuji T, Iryo K, Watanabe N, Tsuji M. Preparation of silver nanoparticles by laser ablation in solution: influence of laser wavelength on particle size. Appl Surf Sci. 2002;202:80–5. 10.1016/S0169-4332(02)00936-4 . Search in Google Scholar

[24] Tsuji T, Kakita T, Tsuji M. Preparation of nano-size particles of silver with femtosecond laser ablation in water. Appl Surf Sci. 2003;206:314–20. 10.1016/S0169-4332(02)01230-8 . Search in Google Scholar

[25] Siegel J, Kvítek O, Ulbrich P, Kolská Z, Slepička P, Švorčík V. Progressive approach for metal nanoparticle synthesis. Mater Lett. 2012;89:47–50. 10.1016/j.matlet.2012.08.048 . Search in Google Scholar

[26] Elsupikhe RF, Shameli K, Ahmad MB, Ibrahim NA, Zainudin N. Green sonochemical synthesis of silver nanoparticles at varying concentrations of κ-carrageenan. Nanoscale Res Lett. 2015;10:302. 10.1186/s11671-015-0916-1 . Search in Google Scholar PubMed PubMed Central

[27] Dubas ST, Kumlangdudsana P, Potiyaraj P. Layer-by-layer deposition of antimicrobial silver nanoparticles on textile fibers. Colloids Surf Physicochem Eng Asp. 2006;289:105–9. 10.1016/j.colsurfa.2006.04.012 . Search in Google Scholar

[28] Pal S, Tak YK, Song JM. Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the Gram-negative bacterium Escherichia coli. Appl Env Microbiol. 2007;73:1712–20. 10.1128/AEM.02218-06 . Search in Google Scholar PubMed PubMed Central

[29] Ali W, Rajendran S, Joshi M. Synthesis and characterization of chitosan and silver loaded chitosan nanoparticles for bioactive polyester. Carbohydr Polym. 2011;83:438–46. 10.1016/j.carbpol.2010.08.004 . Search in Google Scholar

[30] Shrivastava S, Bera T, Roy A, Singh G, Ramachandrarao P, Dash D. Characterization of enhanced antibacterial effects of novel silver nanoparticles. Nanotechnology. 2007;18:225103. 10.1088/0957-4484/18/22/225103 . Search in Google Scholar

[31] Tejamaya M, Römer I, Merrifield RC, Lead JR. Stability of citrate, PVP, and PEG coated silver nanoparticles in ecotoxicology media. Env Sci Technol. 2012;46:7011–7. 10.1021/es2038596 . Search in Google Scholar PubMed

[32] Iravani S. Bacteria in nanoparticle synthesis: current status and future prospects. Int Scholar Res Not. 2014;2014:359316. 10.1155/2014/359316 . Search in Google Scholar PubMed PubMed Central

[33] Makarov VV, Love AJ, Sinitsyna OV, Makarova SS, Yaminsky IV, Taliansky ME, et al. “Green” nanotechnologies: synthesis of metal nanoparticles using plants. Acta Nat. 2014;6(20):35–44. 10.32607/20758251-2014-6-1-35-44 . Search in Google Scholar

[34] Gowramma B, Keerthi U, Rafi M, Rao DM. Biogenic silver nanoparticles production and characterization from native stain of Corynebacterium species and its antimicrobial activity. 3 Biotech. 2015;5:195–201. 10.1007/s13205-014-0210-4 . Search in Google Scholar PubMed PubMed Central

[35] Shah M, Fawcett D, Sharma S, Tripathy SK, Poinern GEJ. Green synthesis of metallic nanoparticles via biological entities. Materials. 2015;8:7278–308. 10.3390/ma8115377 . Search in Google Scholar PubMed PubMed Central

[36] Ahmad S, Munir S, Zeb N, Ullah A, Khan B, Ali J, et al. Green nanotechnology: a review on green synthesis of silver nanoparticles – an ecofriendly approach. Int J Nanomed. 2019;14:5087–107. 10.2147/IJN.S200254 . Search in Google Scholar PubMed PubMed Central

[37] Shahverdi AR, Minaeian S, Shahverdi HR, Jamalifar H, Nohi A-A. Rapid synthesis of silver nanoparticles using culture supernatants of Enterobacteria: a novel biological approach. Process Biochem. 2007;42:919–23. 10.1016/j.procbio.2007.02.005 . Search in Google Scholar

[38] Korbekandi H, Iravani S, Abbasi S. Optimization of biological synthesis of silver nanoparticles using Lactobacillus casei subsp. casei. J Chem Technol Biotechnol. 2012;87:932–7. 10.1002/jctb.3702 . Search in Google Scholar

[39] Liu Y, Fu J, Chen P, Yu X, Yang P. Studies on biosorption of Au3+ by Bacillus megaterium. Wei Sheng Wu Xue Bao. 2000;40:425–9. Search in Google Scholar

[40] Das VL, Thomas R, Varghese RT, Soniya EV, Mathew J, Radhakrishnan EK. Extracellular synthesis of silver nanoparticles by the Bacillus strain CS 11 isolated from industrialized area. 3 Biotech. 2014;4:121–6. 10.1007/s13205-013-0130-8 . Search in Google Scholar PubMed PubMed Central

[41] Guilger-Casagrande M, de Lima R. Synthesis of silver nanoparticles mediated by fungi: a review. Front Bioeng Biotechnol. 2019;7:287. 10.3389/fbioe.2019.00287 . Search in Google Scholar PubMed PubMed Central

[42] Ingle A, Rai M, Gade A, Bawaskar M. Fusarium solani: a novel biological agent for the extracellular synthesis of silver nanoparticles. J Nanopart Res. 2008;11:2079. 10.1007/s11051-008-9573-y . Search in Google Scholar

[43] Syed A, Saraswati S, Kundu GC, Ahmad A. Biological synthesis of silver nanoparticles using the fungus Humicola sp. and evaluation of their cytoxicity using normal and cancer cell lines. Spectrochim Acta A Mol Biomol Spectrosc. 2013;114:144–7. 10.1016/j.saa.2013.05.030 . Search in Google Scholar

[44] Owaid MN, Raman J, Lakshmanan H, Al-Saeedi SSS, Sabaratnam V, Abed IA. Mycosynthesis of silver nanoparticles by Pleurotus cornucopiae var. citrinopileatus and its inhibitory effects against Candida sp. Mater Lett. 2015;153:186–90. 10.1016/j.matlet.2015.04.023 . Search in Google Scholar

[45] Xue B, He D, Gao S, Wang D, Yokoyama K, Wang L. Biosynthesis of silver nanoparticles by the fungus Arthroderma fulvum and its antifungal activity against genera of Candida, Aspergillus and Fusarium. Int J Nanomed. 2016;11:1899–906. 10.2147/IJN.S98339 . Search in Google Scholar

[46] Vigneshwaran N, Ashtaputre NM, Varadarajan PV, Nachane RP, Paralikar KM, Balasubramanya RH. Biological synthesis of silver nanoparticles using the fungus Aspergillus flavus. Mater Lett. 2007;61:1413–8. 10.1016/j.matlet.2006.07.042 . Search in Google Scholar

[47] Bhainsa KC, D’Souza SF. Extracellular biosynthesis of silver nanoparticles using the fungus Aspergillus fumigatus. Colloids Surf B Biointerfaces. 2006;47:160–4. 10.1016/j.colsurfb.2005.11.026 . Search in Google Scholar

[48] Ahmad A, Mukherjee P, Senapati S, Mandal D, Khan MI, Kumar R, et al. Extracellular biosynthesis of silver nanoparticles using the fungus Fusarium oxysporum. Colloids Surf B Biointerfaces. 2003;28:313–8. 10.1016/S0927-7765(02)00174-1 . Search in Google Scholar

[49] Vigneshwaran N, Kathe AA, Varadarajan PV, Nachane RP, Balasubramanya RH. Biomimetics of silver nanoparticles by white rot fungus, Phaenerochaete chrysosporium. Colloids Surf B Biointerfaces. 2006;53:55–9. 10.1016/j.colsurfb.2006.07.014 . Search in Google Scholar PubMed

[50] Korbekandi H, Ashari Z, Iravani S, Abbasi S. Optimization of biological synthesis of silver nanoparticles using Fusarium oxysporum. Iran J Pharm Res IJPR. 2013;12:289–98. 10.1515/gps-2018-0042 . Search in Google Scholar

[51] Hamouda RA, Hussein MH, Abo-elmagd RA, Bawazir SS. Synthesis and biological characterization of silver nanoparticles derived from the cyanobacterium Oscillatoria limnetica. Sci Rep. 2019;9:13071. 10.1038/s41598-019-49444-y . Search in Google Scholar PubMed PubMed Central

[52] Govindaraju K, Kiruthiga V, Kumar VG, Singaravelu G. Extracellular synthesis of silver nanoparticles by a Marine Alga, Sargassum Wightii Grevilli and their antibacterial effects. J Nanosci Nanotechnol. 2009;9:5497–501. 10.1166/jnn.2009.1199 . Search in Google Scholar PubMed

[53] Rajeshkumar S, Malarkodi C, Paulkumar K, Vanaja M, Gnanajobitha G, Annadurai G. Algae mediated green fabrication of silver nanoparticles and examination of its antifungal activity against clinical pathogens. Int J Met. 2014;2014:692643. 10.1155/2014/692643 . Search in Google Scholar

[54] AbdelRahim K, Mahmoud SY, Ali AM, Almaary KS, Mustafa AE-ZMA, Husseiny SM. Extracellular biosynthesis of silver nanoparticles using Rhizopus stolonifer. Saudi J Biol Sci. 2017;24:208–16. 10.1016/j.sjbs.2016.02.025 . Search in Google Scholar PubMed PubMed Central

[55] Salari Z, Danafar F, Dabaghi S, Ataei SA. Sustainable synthesis of silver nanoparticles using macroalgae Spirogyra varians and analysis of their antibacterial activity. J Saudi Chem Soc. 2016;20:459–64. 10.1016/j.jscs.2014.10.004 . Search in Google Scholar

[56] Niknejad F, Nabili M, Daie Ghazvini R, Moazeni M. Green synthesis of silver nanoparticles: advantages of the yeast Saccharomyces cerevisiae model. Curr Med Mycol. 2015;1:17–24. 10.18869/acadpub.cmm.1.3.17 . Search in Google Scholar PubMed PubMed Central

[57] Kowshik M, Ashtaputre S, Kharrazi S, Vogel W, Urban J, Kulkarni SK, et al. Extracellular synthesis of silver nanoparticles by a silver-tolerant yeast strain MKY3. Nanotechnology. 2002;14:95–100. 10.1088/0957-4484/14/1/321 . Search in Google Scholar

[58] Dhuper S, Panda D, Nayak PL. Green synthesis and characterization of zero valent iron nanoparticles from the leaf extract of Mangifera indica. Nano Trends J Nanotechnol App. 2012;13(2):16–22. Search in Google Scholar

[59] Emaga TH, Robert C, Ronkart SN, Wathelet B, Paquot M. Dietary fibre components and pectin chemical features of peels during ripening in banana and plantain varieties. Bioresour Technol. 2008;99:4346–54. 10.1016/j.biortech.2007.08.030 . Search in Google Scholar PubMed

[60] Shaik MR, Khan M, Kuniyil M, Al-Warthan A, Alkhathlan HZ, Siddiqui MR, et al. Plant-extract-assisted green synthesis of silver nanoparticles using Origanum vulgare L. extract and their microbicidal activities. Sustainability. 2018;10:913. 10.3390/su10040913 . Search in Google Scholar

[61] Ahmed S, Saifullah, Ahmad M, Swami BL, Ikram S. Green synthesis of silver nanoparticles using Azadirachta indica aqueous leaf extract. J Radiat Res Appl Sci. 2016;9:1–7. 10.1016/j.jrras.2015.06.006 . Search in Google Scholar

[62] López-Miranda JL, Vázquez M, Fletes N, Esparza R, Rosas G. Biosynthesis of silver nanoparticles using a Tamarix gallica leaf extract and their antibacterial activity. Mater Lett. 2016;176:285–9. 10.1016/j.matlet.2016.04.126 . Search in Google Scholar

[63] Chinnappan S, Kandasamy S, Arumugam S, Seralathan K-K, Thangaswamy S, Muthusamy G. Biomimetic synthesis of silver nanoparticles using flower extract of Bauhinia purpurea and its antibacterial activity against clinical pathogens. Environ Sci Pollut Res. 2018;25:963–9. 10.1007/s11356-017-0841-1 . Search in Google Scholar PubMed

[64] Ibraheim MH, Ibrahiem AA, Dalloul TR. Biosynthesis of silver nanoparticles using Pomegranate juice extract and its antibacterial activity. Int J Appl Sci Biotechnol. 2016;4:254. 10.3126/ijasbt.v4i3.15417 . Search in Google Scholar

[65] Lakshmanan G, Sathiyaseelan A, Kalaichelvan PT, Murugesan K. Plant-mediated synthesis of silver nanoparticles using fruit extract of Cleome viscosa L.: assessment of their antibacterial and anticancer activity. Karbala Int J Mod Sci. 2018;4:61–8. 10.1016/j.kijoms.2017.10.007 . Search in Google Scholar

[66] Prasad T, Elumalai E. Biofabrication of Ag nanoparticles using Moringa oleifera leaf extract and their antimicrobial activity. Asian Pac J Trop Biomed. 2011;1:439–42. 10.1016/S2221-1691(11)60096-8 . Search in Google Scholar

[67] Saxena A, Tripathi RM, Zafar F, Singh P. Green synthesis of silver nanoparticles using aqueous solution of Ficus benghalensis leaf extract and characterization of their antibacterial activity. Mater Lett. 2012;67:91–4. 10.1016/j.matlet.2011.09.038 . Search in Google Scholar

[68] Shankar SS, Ahmad A, Pasricha R, Sastry M. Bioreduction of chloroaurate ions by geranium leaves and its endophytic fungus yields gold nanoparticles of different shapes. J Mater Chem. 2003;13:1822–6. 10.1039/B303808B . Search in Google Scholar

[69] Shankar SS, Ahmad A, Sastry M. Geranium leaf assisted biosynthesis of silver nanoparticles. Biotechnol Prog. 2003;19:1627–31. 10.1021/bp034070w . Search in Google Scholar

[70] Rai A, Singh A, Ahmad A, Sastry M. Role of halide ions and temperature on the morphology of biologically synthesized gold nanotriangles. Langmuir. 2006;22:736–41. 10.1021/la052055q . Search in Google Scholar

[71] Rai A, Chaudhary M, Ahmad A, Bhargava S, Sastry M. Synthesis of triangular Au core–Ag shell nanoparticles. Mater Res Bull. 2007;42:1212–20. 10.1016/j.materresbull.2006.10.019 . Search in Google Scholar

[72] Chandran SP, Chaudhary M, Pasricha R, Ahmad A, Sastry M. Synthesis of gold nanotriangles and silver nanoparticles using aloe vera plant extract. Biotechnol Prog. 2006;22(2):577–83. 10.1021/bp0501423 . Search in Google Scholar

[73] Ponarulselvam S, Panneerselvam C, Murugan K, Aarthi N, Kalimuthu K, Thangamani S. Synthesis of silver nanoparticles using leaves of Catharanthus roseus Linn. G. Don and their antiplasmodial activities. Asian Pac J Trop Biomed. 2012;2(7):574–80. 10.1016/S2221-1691(12)60100-2 . Search in Google Scholar

[74] Durán N, Marcato PD, De Souza GIH, Alves OL, Esposito E. Antibacterial effect of silver nanoparticles produced by fungal process on textile fabrics and their effluent treatment. J Biomed Nanotechnol. 2007;3(2):203–8. 10.1166/jbn.2007.022 . Search in Google Scholar

[75] Zargar M, Hamid AA, Bakar FA, Shamsudin MN, Shameli K, Jahanshiri F, et al. Green synthesis and antibacterial effect of silver nanoparticles using Vitex negundo L. Molecules. 2011;16(8):6667–76. 10.3390/molecules16086667 . Search in Google Scholar PubMed PubMed Central

[76] Kasyanenko N, Varshavskii M, Ikonnikov E, Tolstyko E, Belykh R, Sokolov P, et al. DNA modified with metal nanoparticles: preparation and characterization of ordered metal-DNA nanostructures in a solution and on a substrate. J Nanomater. 2016;2016:3237250. 10.1155/2016/3237250 . Search in Google Scholar

[77] Sastry M, Patil V, Sainkar SR. Electrostatically controlled diffusion of carboxylic acid derivatized silver colloidal particles in thermally evaporated fatty amine films. J Phys Chem B. 1998;102(8):1404–10. 10.1021/jp9719873 . Search in Google Scholar

[78] Li Y, Chen S-M. The electrochemical properties of acetaminophen on bare glassy carbon electrode. Int J Electrochem Sci. 2012;7:13. 10.1016/j.jcis.2016.08.028 . Search in Google Scholar PubMed

[79] Vanden Bout DA. Metal nanoparticles:  synthesis, characterization, and applications. In:  Feldheim DL, Foss CA Jr., editors. New York: Marcel Dekker, c2002.x + 338 pp. $150.00. ISBN:  0-8247-0604-8. J Am Chem Soc 124:7874–75. 10.1504/IJNT.2011.038201 . Search in Google Scholar

[80] Rajeshkumar S, Bharath LV. Mechanism of plant-mediated synthesis of silver nanoparticles – a review on biomolecules involved, characterisation and antibacterial activity. Chem Biol Interact. 2017;273:219–27. 10.1016/j.cbi.2017.06.019 . Search in Google Scholar PubMed

[81] Vijayaraghavan K, Ashok kumar T. Plant-mediated biosynthesis of metallic nanoparticles: a review of literature, factors affecting synthesis, characterization techniques and applications. J Environ Chem Eng. 2017;5(5):4866–83. 10.1016/j.jece.2017.09.026 . Search in Google Scholar

[82] Alexander L, Klug HP. Determination of crystallite size with the X-ray spectrometer. J Appl Phys. 1950;21(2):137–42. 10.1063/1.1699612 . Search in Google Scholar

[83] Prathna TC, Chandrasekaran N, Raichur AM, Mukherjee A. Biomimetic synthesis of silver nanoparticles by Citrus limon (lemon) aqueous extract and theoretical prediction of particle size. Colloids Surf B Biointerfaces. 2011;82(1):152–9. 10.1016/j.colsurfb.2010.08.036 . Search in Google Scholar PubMed

[84] Sharma R, Bisen DP, Shukla U, Sharma BG. X-ray diffraction: a powerful method of characterizing nanomaterials. Recent Res Sci Technol. 2012;4:77–9. 10.3390/cryst6080087 . Search in Google Scholar

[85] Rohman A, Man YBC. Fourier transform infrared (FTIR) spectroscopy for analysis of extra virgin olive oil adulterated with palm oil. Food Res Int. 2010;43(3):886–92. 10.1016/j.foodres.2009.12.006 . Search in Google Scholar

[86] Noruzi M. Biosynthesis of gold nanoparticles using plant extracts. Bioprocess Biosyst Eng. 2015;38(1):1–14. 10.1016/j.mspro.2015.11.113 . Search in Google Scholar

[87] Noruzi M, Zare D, Khoshnevisan K, Davoodi D. Rapid green synthesis of gold nanoparticles using Rosa hybrida petal extract at room temperature. Spectrochim Acta A Mol Biomol Spectrosc. 2011;79(5):1461–5. 10.1016/j.saa.2011.05.001 . Search in Google Scholar

[88] Sundrarajan M, Gowri S. Green synthesis of titanium dioxide nanoparticles by nyctanthes arbor tristis leaves extract. Chalcogenide Lett. 2011;8:447–51. 10.1016/S1995-7645(14)60171-1 . Search in Google Scholar

[89] Hudlikar M, Joglekar S, Dhaygude M, Kodam K. Green synthesis of TiO2 nanoparticles by using aqueous extract of Jatropha curcas L. latex. Mater Lett. 2012;75:196–9. 10.1016/j.matlet.2012.02.018 . Search in Google Scholar

[90] Rahimi-Nasrabadi M, Pourmortazavi SM, Shandiz SAS, Ahmadi F, Batooli H. Green synthesis of silver nanoparticles using Eucalyptus leucoxylon leaves extract and evaluating the antioxidant activities of extract. Nat Prod Res. 1969;28(22):1964–9. 10.1080/14786419.2014.918124 . Search in Google Scholar PubMed

[91] Zhang M, Zhang K, Gusseme BD, Verstraete W, Field R. The antibacterial and anti-biofouling performance of biogenic silver nanoparticles by Lactobacillus fermentum. Biofouling. 2014;30(3):347–57. 10.1080/08927014.2013.873419 . Search in Google Scholar PubMed

[92] Roy A, Bulut O, Some S, Kumar Mandal A, Deniz Yilmaz M. Green synthesis of silver nanoparticles: biomolecule–nanoparticle organizations targeting antimicrobial activity. RSC Adv. 2019;9(5):2673–702. 10.1039/c8ra08982e . Search in Google Scholar PubMed PubMed Central

[93] Ghosh S, Patil S, Ahire M, Kitture R, Kale S, Pardesi K, et al. Synthesis of silver nanoparticles using Dioscorea bulbifera tuber extract and evaluation of its synergistic potential in combination with antimicrobial agents. Int J Nanomed. 2012;7:483–96. 10.2147/IJN.S24793 . Search in Google Scholar PubMed PubMed Central

[94] Eppler AS, Rupprechter G, Anderson EA, Somorjai GA. Thermal and chemical stability and adhesion strength of Pt nanoparticle arrays supported on silica studied by transmission electron microscopy and atomic force microscopy. J Phys Chem B. 2000;104(31):7286–92. 10.1021/jp0006429 . Search in Google Scholar

[95] Phenrat T, Kim HJ, Fagerlund F, Illangasekare T, Tilton RD, Lowry GV. Particle size distribution, concentration, and magnetic attraction affect transport of polymer-modified Fe0 nanoparticles in sand columns. Environ Sci Technol. 2009;43(13):5079–85. 10.1021/es900171v . Search in Google Scholar

[96] Goon IY, Lai LMH, Lim M, Munroe P, Gooding JJ, Amal R. Fabrication and dispersion of gold-shell-protected magnetite nanoparticles: systematic control using polyethyleneimine. Chem Mater. 2009;21(4):673–81. 10.1021/cm8025329 . Search in Google Scholar

[97] Niehus H, Heiland W, Taglauer E. Low-energy ion scattering at surfaces. Surf Sci Rep. 1993;17(4):213–303. 10.1016/0167-5729(93)90024-J . Search in Google Scholar

[98] Brongersma HH, Draxler M, de Ridder M, Bauer P. Surface composition analysis by low-energy ion scattering. Surf Sci Rep. 2007;62(3):63–109. 10.1016/j.surfrep.2006.12.002 . Search in Google Scholar

[99] Al-Hada M, Gregoratti L, Amati M, Neeb M. Pristine and oxidised Ag-nanoparticles on free-standing graphene as explored by X-ray photoelectron and Auger spectroscopy. Surf Sci. 2020;693:121533. 10.1016/j.susc.2019.121533 . Search in Google Scholar

[100] Goebl D, Bruckner B, Roth D, Ahamer C, Bauer P. Low-energy ion scattering: a quantitative method? Nucl Instrum Methods Phys Re Sect B Beam Interact Mater At. 2015;354:3–8. 10.1016/j.nimb.2014.11.030 . Search in Google Scholar

[101] Rafati A, ter Veen R, Castner DG. Low-energy ion scattering: Determining overlayer thickness for functionalized gold nanoparticles. Surf Interface Anal. 2013;45(11–12):1737–41. 10.1002/sia.5315 . Search in Google Scholar PubMed PubMed Central

[102] Ecke G, Cimalla V, Tonisch K, Lebedev V, Romanus H, Ambacher O, et al. Analysis of nanostructures by means of auger electron spectroscopy. 2007;58(6):6. Search in Google Scholar

[103] Mogk DW. Application of Auger electron spectroscopy to studies of chemical weathering. Rev Geophys. 1990;28(4):337–56. 10.1029/RG028i004p00337 . Search in Google Scholar

[104] Patra JK, Baek KH. Green nanobiotechnology: factors affecting synthesis and characterization techniques. J Nanomater. 2014;2014:417305. 10.1155/2014/417305 . Search in Google Scholar

[105] Dankovich TA, Gray DG. Bactericidal paper impregnated with silver nanoparticles for point-of-use water treatment. Environ Sci Technol. 2011;45(5):1992–8. 10.1021/es103302t . Search in Google Scholar PubMed

[106] Mohammed Fayaz A, Balaji K, Kalaichelvan PT, Venkatesan R. Fungal based synthesis of silver nanoparticles – an effect of temperature on the size of particles. Colloids Surf B Biointerfaces. 2009;74:123–6. 10.1016/j.colsurfb.2009.07.002 . Search in Google Scholar PubMed

[107] Roopan SM, Bharathi A, Abdul Rahuman A, Kamaraj C, Madhumita G, Rohit, et al. Low-cost and eco-friendly phyto-synthesis of silver nanoparticles using Cocos nucifera coir extract and its larvicidal activity. Ind Crop Prod. 2013;43:631–5. 10.1016/j.indcrop.2012.08.013 . Search in Google Scholar

[108] Sadeghi B, Gholamhoseinpoor F. A study on the stability and green synthesis of silver nanoparticles using Ziziphora tenuior (Zt) extract at room temperature. Spectrochim Acta A Mol Biomol Spectrosc. 2015;134:310–5. 10.1016/j.saa.2014.06.046 . Search in Google Scholar PubMed

[109] Tagad CK, Dugasani SR, Aiyer R, Park S, Kulkarni A, Sabharwal S. Green synthesis of silver nanoparticles and their application for the development of optical fiber based hydrogen peroxide sensor. Sens Actuators, B Chem. 2013;183:144–9. 10.1016/j.snb.2013.03.106 . Search in Google Scholar

[110] Akbari B, Pirhadi Tavandashti M, Zandrahimi M. Particle size characterization of nanoparticles – a practical approach. Iran J Mater Sci Eng. 2011;8(2):48–56. 10.1007/978-3-030-39246-8_17 . Search in Google Scholar

[111] Deshmukh SP, Patil SM, Mullani SB, Delekar SD. Silver nanoparticles as an effective disinfectant: a review. Mater Sci Eng C Mater Biol Appl. 2019;97:954–65. 10.1016/j.msec.2018.12.102 . Search in Google Scholar PubMed PubMed Central

[112] Verma P, Maheshwari SK. Applications of silver nanoparticles in diverse sectors. Int J Nano Dimens. 2019;10(1):8–36. 10.22034/ijnd.2018.87646.1609 . Search in Google Scholar

[113] Pulit-Prociak J, Banach M. Silver nanoparticles  – a material for the future? Open Chem. 2016;14:76–91. 10.1515/chem-2016-0005 . Search in Google Scholar

[114] Haider A, Kang I-K. Preparation of silver nanoparticles and their industrial and biomedical applications: a comprehensive review. Adv Mater Sci Eng. 2015;2015:165257. 10.1155/2015/165257 . Search in Google Scholar

[115] Mishra S, Keswani C, Abhilash PC, Fraceto LF, Singh HB. Integrated approach of agri-nanotechnology: challenges and future trends. Front Plant Sci. 2017;8:471. 10.3389/fpls.2017.00471 . Search in Google Scholar PubMed PubMed Central

[116] Paladini F, Pollini M. Antimicrobial silver nanoparticles for wound healing application: progress and future trends. Materials. 2019;12:2540. 10.3390/ma12162540 . Search in Google Scholar PubMed PubMed Central

[117] Mikolajczuk-Szczyrba A, Kieliszek M, Liviu G, Sokolowska B. Characteristics and application of silver nanoparticles in the food industry – review. Carpath J Food Sci Technol. 2019;11:153–60. 10.34302/2019.11.4.14 . Search in Google Scholar

[118] Suriyakalaa U, Antony JJ, Suganya S, Siva D, Sukirtha R, Kamalakkanan S, et al. Hepatocurative activity of biosynthesized silver nanoparticles fabricated using Andrographis paniculata. Colloids Surf B Biointerfaces. 2013;102:189–94. 10.1016/j.colsurfb.2012.06.039 . Search in Google Scholar PubMed

[119] Sun RW-Y, Chen R, Chung NP-Y, Ho C-M, Lin C-LS, Che C-M. Silver nanoparticles fabricated in Hepes buffer exhibit cytoprotective activities toward HIV-1 infected cells. Chem Commun. 2005;40:5059–61. 10.1039/b510984a . Search in Google Scholar PubMed

[120] Lara HH, Ayala-Nuñez NV, Ixtepan-Turrent L, Rodriguez-Padilla C. Mode of antiviral action of silver nanoparticles against HIV-1. J Nanobiotechnol. 2010;8(1):1. 10.1186/1477-3155-8-1 . Search in Google Scholar PubMed PubMed Central

[121] Rogers JV, Parkinson CV, Choi YW, Speshock JL, Hussain SM. A preliminary assessment of silver nanoparticle inhibition of monkeypox virus plaque formation. Nanoscale Res Lett. 2008;3:129–33. 10.1007/s11671-008-9128-2 . Search in Google Scholar

[122] Speshock JL, Murdock RC, Braydich-Stolle LK, Schrand AM, Hussain SM. Interaction of silver nanoparticles with Tacaribe virus. J Nanobiotechnol. 2010;8(1):19. 10.1186/1477-3155-8-19 . Search in Google Scholar PubMed PubMed Central

[123] Park S, Park H, Kim SY, Kim SJ, Woo K, Ko G. Antiviral properties of silver nanoparticles on a magnetic hybrid colloid. Appl Env Microbiol. 2014;80(8):2343–50. 10.1128/AEM.03427-13 . Search in Google Scholar PubMed PubMed Central

[124] Bankar A, Joshi B, Kumar AR, Zinjarde S. Banana peel extract mediated novel route for the synthesis of silver nanoparticles. Colloids Surf Physicochem Eng Asp. 2010;368(1):58–63. 10.1016/j.colsurfa.2010.07.024 . Search in Google Scholar

[125] Raut RW, Mendhulkar VD, Kashid SB. Photosensitized synthesis of silver nanoparticles using Withania somnifera leaf powder and silver nitrate. J Photochem Photobiol B. 2014;132:45–55. 10.1016/j.jphotobiol.2014.02.001 . Search in Google Scholar PubMed

[126] Kim KJ, Sung WS, Suh BK, Moon SK, Choi J-S, Kim JG, et al. Antifungal activity and mode of action of silver nano-particles on Candida albicans. BioMetals. 2009;22(2):235–42. 10.1007/s10534-008-9159-2 . Search in Google Scholar PubMed

[127] Esteban-Tejeda L, Malpartida F, Esteban-Cubillo A, Pecharromán C, Moya JS. Antibacterial and antifungal activity of a soda-lime glass containing copper nanoparticles. Nanotechnology. 2009;20(50):505701. 10.1088/0957-4484/20/50/505701 . Search in Google Scholar PubMed

[128] Gajbhiye M, Kesharwani J, Ingle A, Gade A, Rai M. Fungus-mediated synthesis of silver nanoparticles and their activity against pathogenic fungi in combination with fluconazole. Nanomed Nanotechnol Biol Med. 2009;5(4):382–6. 10.1016/j.nano.2009.06.005 . Search in Google Scholar PubMed

[129] Ogar A, Tylko G, Turnau K. Antifungal properties of silver nanoparticles against indoor mould growth. Sci Total Environ. 2015;521–2:305–14. 10.1016/j.scitotenv.2015.03.101 . Search in Google Scholar PubMed

[130] Gopinath V, Velusamy P. Extracellular biosynthesis of silver nanoparticles using Bacillus sp. GP-23 and evaluation of their antifungal activity towards Fusarium oxysporum. Spectrochim Acta A Mol Biomol Spectrosc. 2013;106:170–4. 10.1016/j.saa.2012.12.087 . Search in Google Scholar PubMed

[131] Abdelghany TM, Al-Rajhi AMH, Abboud MAAM, Alawlaqi MM, Ganash A, Hemy EAM. Recent advances in green synthesis of silver nanoparticles and their applications: about future directions. A review. BioNanoScience. 2018;8(1):5–16. 10.1007/s12668-017-0413-3 . Search in Google Scholar

[132] Jalal M, Ansari MA, Alzohairy MA, Ali SG, Khan HM, Almatroudi A, et al. Biosynthesis of silver nanoparticles from Oropharyngeal Candida glabrata isolates and their antimicrobial activity against clinical strains of bacteria and fungi. Nanomaterials. 2018;8(8):586. 10.3390/nano8080586 . Search in Google Scholar PubMed PubMed Central

[133] Jalal M, Ansari MA, Alzoaihry MA, Ali SG, Khan HM, Almatroudi A, et al. Anticandidal activity of biosynthesized silver nanoparticles: effect on growth, cell morphology, and key virulence attributes of Candida species. Int J Nanomed. 2019;14:4667–79. 10.2147/IJN.S210449 . Search in Google Scholar PubMed PubMed Central

[134] Suresh G, Gunasekar PH, Kokila D, Prabhu D, Dinesh D, Ravichandran N, et al. Green synthesis of silver nanoparticles using Delphinium denudatum root extract exhibits antibacterial and mosquito larvicidal activities. Spectrochim Acta A Mol Biomol Spectrosc. 2014;127:61–6. 10.1016/j.saa.2014.02.030 . Search in Google Scholar PubMed

[135] Tarannum N, Divya, Gautam YK. Facile green synthesis and applications of silver nanoparticles: a state-of-the-art review. RSC Adv. 2019;9(60):34926–48. 10.1039/C9RA04164H . Search in Google Scholar

[136] Allahverdiyev AM, Abamor ES, Bagirova M, Ustundag CB, Kaya C, Kaya F, et al. Antileishmanial effect of silver nanoparticles and their enhanced an/tiparasitic activity under ultraviolet light. Int J Nanomed. 2011;6:2705–14. 10.2147/IJN.S23883 Search in Google Scholar

[137] Saad AHA, Soliman MI, Azzam AM, Mostafa AB. Antiparasitic activity of silver and copper oxide nanoparticles against entamoeba histolytica and cryptosporidium parvum cysts. J Egypt Soc Parasitol. 2015;240(2496):1–10. 10.12816/0017920 . Search in Google Scholar

[138] Du J, Hu Z, Yu Z, Li H, Pan J, Zhao D, et al. Antibacterial activity of a novel Forsythia suspensa fruit mediated green silver nanoparticles against food-borne pathogens and mechanisms investigation. Mater Sci Eng C. 2019;102:247–53. 10.1016/j.msec.2019.04.031 . Search in Google Scholar

[139] Faghri Zonooz N, Salouti M. Extracellular biosynthesis of silver nanoparticles using cell filtrate of Streptomyces sp. ERI-3. Sci Iran. 2011;18(6):1631–5. 10.1016/j.scient.2011.11.029 . Search in Google Scholar

[140] Mukunthan K, Elumalai E, Patel TN, Murty VR. Catharanthus roseus: a natural source for the synthesis of silver nanoparticles. Asian Pac J Trop Biomed. 2011;1(4):270–4. 10.1016/S2221-1691(11)60041-5 . Search in Google Scholar

[141] Dehnavi AS, Raisi A, Aroujalian A. Control size and stability of colloidal silver nanoparticles with antibacterial activity prepared by a green synthesis method. Synth React Inorg Met-Org Nano-Met Chem. 2013;43(5):543–51. 10.1080/15533174.2012.741182 . Search in Google Scholar

[142] Khalil MMH, Ismail EH, El-Baghdady KZ, Mohamed D. Green synthesis of silver nanoparticles using olive leaf extract and its antibacterial activity. Arab J Chem. 2014;7(6):1131–9. 10.1016/j.arabjc.2013.04.007 . Search in Google Scholar

[143] Nanda A, Saravanan M. Biosynthesis of silver nanoparticles from Staphylococcus aureus and its antimicrobial activity against MRSA and MRSE. Nanomed Nanotechnol Biol Med. 2009;5(4):452–6. 10.1016/j.nano.2009.01.012 . Search in Google Scholar PubMed

[144] Gurunathan S, Han JW, Kwon D-N, Kim JH. Enhanced antibacterial and anti-biofilm activities of silver nanoparticles against Gram-negative and Gram-positive bacteria. Nanoscale Res Lett. 2014;9(1):373. 10.1186/1556-276X-9-373 . Search in Google Scholar PubMed PubMed Central

[145] Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, Ramirez JT, et al. The bactericidal effect of silver nanoparticles. Nanotechnology. 2005;16(10):2346–53. 10.1088/0957-4484/16/10/059 . Search in Google Scholar PubMed

[146] Qasim M, Udomluck N, Chang J, Park H, Kim K. Antimicrobial activity of silver nanoparticles encapsulated in poly-N-isopropylacrylamide-based polymeric nanoparticles. Int J Nanomed. 2018;13:235–49. 10.2147/IJN.S153485 . Search in Google Scholar PubMed PubMed Central

[147] Leudjo Taka A, Pillay K, Yangkou Mbianda X. Nanosponge cyclodextrin polyurethanes and their modification with nanomaterials for the removal of pollutants from waste water: a review. Carbohydr Polym. 2017;159:94–107. 10.1016/j.carbpol.2016.12.027 . Search in Google Scholar PubMed

[148] Tran QH, Nguyen VQ, Le A-T. Silver nanoparticles: synthesis, properties, toxicology, applications and perspectives. Adv Nat Sci Nanosci Nanotechnol. 2013;4(3):033001. 10.1088/2043-6262/4/3/033001 . Search in Google Scholar

[149] Ren J, Han P, Wei H, Jia L. Fouling-resistant behavior of silver nanoparticle-modified surfaces against the bioadhesion of microalgae. ACS Appl Mater Interfaces. 2014;6(6):3829–38. 10.1021/am500292y . Search in Google Scholar PubMed

[150] Johania K, Hu H, Santos L, Schiller S, Deva AK, Whiteley G, et al. Determination of bacterial species present in biofilm contaminating the channels of clinical endoscopes. Infect Dis Health. 2018;23(4):189–96. 10.1016/j.idh.2018.06.003 . Search in Google Scholar

[151] Chen M, Yu Q, Sun H. Novel strategies for the prevention and treatment of biofilm related infections. Int J Mol Sci. 2013;14(9):18488–501. 10.3390/ijms140918488 . Search in Google Scholar PubMed PubMed Central

[152] Desrousseaux C, Sautou V, Descamps S, Traoré O. Modification of the surfaces of medical devices to prevent microbial adhesion and biofilm formation. J Hosp Infect. 2013;85(2):87–93. 10.1016/j.jhin.2013.06.015 . Search in Google Scholar PubMed

[153] Ramachandran R, Sangeetha D. Antibiofilm efficacy of silver nanoparticles against biofilm forming multidrug resistant clinical isolates. Pharma Innov. 2017;6(11):36–43. Search in Google Scholar

[154] Martinez-Gutierrez F, Boegli L, Agostinho A, Sánchez EM, Bach H, Ruiz F, et al. Anti-biofilm activity of silver nanoparticles against different microorganisms. Biofouling. 2013;29(6):651–60. 10.1080/08927014.2013.794225 . Search in Google Scholar PubMed

[155] Palanisamy NK, Ferina N, Amirulhusni AN, Mohd-Zain Z, Hussaini J, Ping LJ, et al. Antibiofilm properties of chemically synthesized silver nanoparticles found against Pseudomonas aeruginosa. J Nanobiotechnol. 2014;12(1):2. 10.1186/1477-3155-12-2 . Search in Google Scholar PubMed PubMed Central

[156] Fabrega J, Renshaw JC, Lead JR. Interactions of silver nanoparticles with Pseudomonas putida biofilms. Environ Sci Technol. 2009;43(23):9004–9. 10.1021/es901706j . Search in Google Scholar PubMed

[157] Kalishwaralal K, BarathManiKanth S, Pandian SR, Deepak V, Gurunathan S. Silver nanoparticles impede the biofilm formation by Pseudomonas aeruginosa and Staphylococcus epidermidis. Colloids Surf B Biointerfaces. 2010;79(2):340–4. 10.1016/j.colsurfb.2010.04.014 . Search in Google Scholar PubMed

[158] Mohanty S, Mishra S, Jena P, Jacob B, Sarkar B, Sonawane A. An investigation on the antibacterial, cytotoxic, and antibiofilm efficacy of starch-stabilized silver nanoparticles. Nanomed Nanotechnol Biol Med. 2012;8(6):916–24. 10.1016/j.nano.2011.11.007 . Search in Google Scholar PubMed

[159] Nayak BS, Sandiford S, Maxwell A. Evaluation of the wound-healing activity of ethanolic extract of Morinda citrifolia L. leaf. Evid-based Complement Alternat Med. 2009;1(6):351–6. 10.1093/ecam/nem127 . Search in Google Scholar PubMed PubMed Central

[160] Rigo C, Ferroni L, Tocco I, Roman M, Munivrana I, Gardin C, et al. Active silver nanoparticles for wound healing. Int J Mol Sci. 2013;14(3):4817–40. 10.3390/ijms14034817 . Search in Google Scholar PubMed PubMed Central

[161] Ahmadi M, Adibhesami M. The effect of silver nanoparticles on wounds contaminated with Pseudomonas aeruginosa in mice: an experimental study. Iran J Pharm Res IJPR. 2017;16(2):661. 10.22037/IJPR.2017.2023 . Search in Google Scholar

[162] Rujitanaroj P, Pimpha N, Supaphol P. Wound-dressing materials with antibacterial activity from electrospun gelatin fiber mats containing silver nanoparticles. Polymer. 2008;49(21):4723–32. 10.1016/j.polymer.2008.08.021 . Search in Google Scholar

[163] Miller CN, Newall N, Kapp SE, Lewin G, Karimi L, Carville K, et al. A randomized-controlled trial comparing cadexomer iodine and nanocrystalline silver on the healing of leg ulcers. Wound Repair Regenerat. 2010;18(4):359–67. 10.1111/j.1524-475X.2010.00603.x . Search in Google Scholar PubMed

[164] Sriram MI, Kanth SBM, Kalishwaralal K, Gurunathan S. Antitumor activity of silver nanoparticles in Dalton’s lymphoma ascites tumor model. Int J Nanomed. 2010;5:753–62. 10.2147/IJN.S11727 . Search in Google Scholar PubMed PubMed Central

[165] Foldbjerg R, Irving ES, Hayashi Y, Sutherland DS, Thorsen K, Autrup H, et al. Global gene expression profiling of human lung epithelial cells after exposure to nanosilver. Toxicol Sci. 2012;130(1):145–57. 10.1093/toxsci/kfs225 . Search in Google Scholar PubMed

[166] Lin J, Huang Z, Wu H, Zhou W, Jin P, Wei P, et al. Inhibition of autophagy enhances the anticancer activity of silver nanoparticles. Autophagy. 2014;10(11):2006–20. 10.4161/auto.36293 . Search in Google Scholar

[167] Sankar R, Karthik A, Prabu A, Karthik S, Shivashangari KS, Ravikumar V. Origanum vulgare mediated biosynthesis of silver nanoparticles for its antibacterial and anticancer activity. Colloids Surf B Biointerfaces. 2013;108:80–4. 10.1016/j.colsurfb.2013.02.033 . Search in Google Scholar

[168] Castro-Aceituno V, Ahn S, Simu SY, Singh P, Mathiyalagan R, Lee HA, et al. Anticancer activity of silver nanoparticles from Panax ginseng fresh leaves in human cancer cells. Biomed Pharmacother. 2016;84:158–65. 10.1016/j.biopha.2016.09.016 . Search in Google Scholar

[169] Khateef R, Khadri H, Almatroudi A, Alsuhaibani SA, Mobeen SA, Khan RA. Potential in-vitro anti-breast cancer activity of green-synthesized silver nanoparticles preparation against human MCF-7 cell-lines. Adv Nat Sci Nanosci Nanotechnol. 2019;10(4):045012. 10.1088/2043-6254/ab47ff . Search in Google Scholar

[170] Tomlinson E. Theory and practice of site-specific drug delivery. Adv Drug Delivery Rev. 1987;1(2):87–198. 10.1016/0169-409X(87)90001-9 . Search in Google Scholar

[171] Jensen SA, Day ES, Ko CH, Hurley LA, Luciano JP, Kouri FM, et al. Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci Translat Med. 2013;5(209):209ra152. 10.1126/scitranslmed.3006839 . Search in Google Scholar PubMed PubMed Central

[172] Lee JS, Lytton-Jean AK, Hurst SJ, Mirkin CA. Silver nanoparticle−oligonucleotide conjugates based on DNA with triple cyclic disulfide moieties. Nano Lett. 2007;7(7):2112–5. 10.1021/nl071108g . Search in Google Scholar PubMed PubMed Central

[173] Benyettou F, Rezgui R, Ravaux F, Jaber T, Blumer K, Jouiad M, et al. Synthesis of silver nanoparticles for the dual delivery of doxorubicin and alendronate to cancer cells. J Mater Chem B. 2015;3(36):7237–45. 10.1039/C5TB00994D . Search in Google Scholar PubMed

[174] Ding Q, Liu D, Guo D, Yang F, Pang X, Che R, et al. Shape-controlled fabrication of magnetite silver hybrid nanoparticles with high performance magnetic hyperthermia. Biomaterials. 2017;124:35–46. 10.1016/j.biomaterials.2017.01.043 . Search in Google Scholar PubMed

[175] Nam KY. In vitro antimicrobial effect of the tissue conditioner containing silver nanoparticles. J Adv prosthodontics. 2011;3(1):20–4. 10.4047/jap.2011.3.1.20 . Search in Google Scholar PubMed PubMed Central

[176] Manikandan V, Velmurugan P, Park JH, Chang WS, Park YJ, Jayanthi PC, et al. Green synthesis of silver oxide nanoparticles and its antibacterial activity against dental pathogens. 3 Biotech. 2017;7(1):72. 10.1007/s13205-017-0670-4 . Search in Google Scholar PubMed PubMed Central

[177] Pérez-Díaz MA, Boegli L, James G, Velasquillo C, Sanchez-Sanchez R, Martinez-Martinez RE, et al. Silver nanoparticles with antimicrobial activities against Streptococcus mutans and their cytotoxic effect. Mater Sci Eng C. 2015;55:360–6. 10.1016/j.msec.2015.05.036 . Search in Google Scholar PubMed

[178] Santos VE, Targino AG, Flores MA, Pessoa HD, Galembeck A, Rosenblatt A. Antimicrobial activity of silver nanoparticles in treating dental caries. Rev da Fac de Odontologia-UPF. 2013;18(3):312–5. 10.5335/rfo.v18i3.3568 . Search in Google Scholar

[179] Bharti A, Singh S, Meena VK, Goyal N. Structural characterization of silver-hydroxyapatite nanocomposite: a bone repair biomaterial. Mater Today Proc. 2016;3:2113–20. 10.1016/j.matpr.2016.04.116 . Search in Google Scholar

[180] Zhou K, Dong C, Zhang X, Shi L, Chen Z, Xu Y, et al. Preparation and characterization of nanosilver-doped porous hydroxyapatite scaffolds. Ceram Int. 2015;41(1):1671–6. 10.1016/j.ceramint.2014.09.108 . Search in Google Scholar

[181] Ciobanu CS, Iconaru SL, Pasuk I, Vasile BS, Lupu AR, Hermenean A, et al. Structural properties of silver doped hydroxyapatite and their biocompatibility. Mater Sci Eng C. 2013;33(3):1395–402. 10.1016/j.msec.2012.12.042 . Search in Google Scholar PubMed

[182] Ramirez-Lee MA, Aguirre-Bañuelos P, Martinez-Cuevas PP, Espinosa-Tanguma R, Chi-Ahumada E, Martinez-Castañon GA, et al. Evaluation of cardiovascular responses to silver nanoparticles (AgNPs) in spontaneously hypertensive rats. Nanomed Nanotechnol Biol Med. 2018;14(2):385–95. 10.1016/j.nano.2017.11.013 . Search in Google Scholar PubMed

[183] Almofti MR, Ichikawa T, Yamashita K, Terada H, Shinohara Y. Silver ion induces a cyclosporine A-insensitive permeability transition in rat liver mitochondria and release of apoptogenic cytochrome c. J Biochem. 2003;134:43–9. 10.1093/jb/mvg111 . Search in Google Scholar PubMed

[184] Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol Vitro. 2005;7:975–83. 10.1016/j.tiv.2005.06.034 . Search in Google Scholar PubMed

[185] Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann MC. In Vitro cytotoxicity of nanoparticles in Mammalian Germline stem cells. Toxicol Sci. 2005;88:412–9. 10.1093/toxsci/kfi256 Search in Google Scholar PubMed PubMed Central

[186] Laban G, Nies LF, Turco RF, Bickham JW, Sepúlveda MS. The effects of silver nanoparticles on fathead minnow (Pimephales promelas) embryos. Ecotoxicology. 2010;19(1):185–95. 10.1007/s10646-009-0404-4 . Search in Google Scholar PubMed

[187] Sung JH, Ji JH, Yoon JU, Kim DS, Song MY, Jeong J, et al. Lung function changes in Sprague-Dawley rats after prolonged inhalation exposure to silver nanoparticles. Inhal Toxicol. 2008;20(6):567–74. 10.1080/08958370701874671 . Search in Google Scholar PubMed

[188] Cho YM, Mizuta Y, Akagi JI, Toyoda T, Sone M, Ogawa K. Size-dependent acute toxicity of silver nanoparticles in mice. J Toxicol Pathol. 2018;31(1):73–80. 10.1293/tox.2017-0043 . Search in Google Scholar PubMed PubMed Central

© 2020 Ahmad Almatroudi, published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

• X / Twitter

Supplementary Materials

Please login or register with De Gruyter to order this product.

Journal and Issue

Articles in the same issue.

Blended Copper and Nano-Silver Screen-Printed Circuits on FTO-Coated Glass

• Abbas, Bahaa
• Jewell, Eifion
• Searle, Justin

Using a mixture of micro-copper and nano-silver in the production of screen-printed circuits has the potential to reduce material costs and cost variability. The fundamental premise of this study involved dispersing silver nanoparticles among the larger copper microparticles at selected ratios and subsequently sintering in order to establish their resultant electrical and physical performance. Commercial materials were mixed, printed, and sintered at two thermal regimes on fluorine-doped tin oxide (FTO)-coated glass substrate. The inclusion of 25% silver provided an appreciable reduction in electrical resistance from 4.21 Ω to 0.93 Ω, with further silver additions having less impact. The thermal regime used for sintering had a secondary impact on the final electrical performance. The addition of silver reduced the adhesion to the FTO substrate, with reduced film integrity. The results show that blending inks offers the advantage of enhancing material conductivity while simultaneously reducing costs, making it a compelling area for exploration and advancement in the field of electronics manufacturing.

• Nano silver;
• copper inks;
• conductive ink;