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European Journal of Nanomedicine

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Effects of silver nanoparticles on human health

Mitra Korani
  • Faculty of Medicine, Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran
  • BuAli Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  • Other articles by this author:
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/ Elham Ghazizadeh
  • BuAli Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  • Biotechnology Research Center, Department of Molecular Genetic, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
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/ Shahla Korani
  • Medical Biology Research Center, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; and Research Institute for Endocrine Science (RIES) , Shahid Beheshti University of Medical Sciences, Tehran, Iran
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/ Zahra Hami
  • Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
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/ Afshin Mohammadi-Bardbori
  • Corresponding author
  • Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, 7146864685 Shiraz, Iran
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Published Online: 2015-01-17 | DOI: https://doi.org/10.1515/ejnm-2014-0032

Abstract

There has been a great deal of attention and research devoted on nanoparticels (NPs) over the last 10 years. From current knowledge in the field of nanotoxicology, it has become evident that the most NPs, if not all are more toxic than bulk materials. The rapid progress and developing has been leading to concerns about the potential risk associated with the use and application of NPs on human health and the environment. Silver nanoparticles (SNPs) are one of the most available and commercially distributed nanomaterials around the world. In order to understand how human health can be affected by SNPs, quantification and detection of SNPs in biological systems have to be conducted in different models. It seems that respiratory and gastrointestinal systems as well as the skin are the major routes of SNPs penetration into the body. Research on SNPs toxicity is mostly conducted in vitro, and the available human and animal data are relatively limited. This review attempts to focus on the characterization and quantification of the potential harmful effects of SNPs on human health.

Keywords: gastrointestinal toxicity; genotoxicity and carcinogenicity; immune system toxicity; kidney toxicity; liver toxicity; lung toxicity; muscle toxicity; nervous system toxicity; reproductive and developmental toxicity; silver nanoparticles (SNPs); skin toxicity

Introduction

Silver nanoparticles (SNPs) refer to the metallic silver with a size of 1–100 nm. The most common sources of SNPs are inorganic salts (1). In certain applications, the antibacterial activities of SNPs are significantly higher than its equivalent metal salt (2). Based on the method of production, SNP molecules are varied in structure and architecture, from oval, triangular, hexagonal shape to nano-wire forms (3). SNPs can be synthesized by traditional methods as well as an alternative method so-called biogenic or green NPs synthesis (4). Recently, many bacterial species, fungi, algae and plants are employed to produce clean, nontoxic, biocompatible and environmentally friendly SNPs (5–9). The advantage of biogenic SNPs are that the molecule can be coated with proteins (secreted by microorganisms such as fungi) allowing them more stable in the aqueous solutions (10).

Antimicrobial uses and antimicrobial resistances of SNPs

SNPs are widely used as potent antimicrobial agents in cosmetic and hygienic products (11, 12). On the other hand, silver-containing materials can be employed to eliminate microorganisms (13, 14). Despite of frequently using, the mechanism action of nanoparticles (NPs) as bactericides in aqueous solutions and solid media is not well known. The antibacterial activity is caused by release of silver cation from the nano-structured surface (15). The high reactivity of NPs might be due to the large surface compared to the low volume ratio (16). In general, the antimicrobial activity of NPs is linked to their ability to alter the cellular permeability and produce reactive oxygen species (ROS) (17, 18). It seems that SNPs below 10 nm are able to penetrate into cytoplasm and disrupt cellular metabolism and inhibit biochemical processes (19, 20). For instance, silver fungicides are able to destroy cell wall and membranes of fungi (21–24). Antimicrobial activities of SNPs are not limited to the bacteria and fungi, as SNPs are useful against other organisms like viruses (25). Besides, SNPs may be applied to reduce insect populations such as Aedes species because they have potential larvicidal activity (26).

SNPs have become one of the most commonly used NPs in commercial products (27). Colloidal solutions of SNPs directly bound to the solid surface of materials and inhibit the growth of highly multi-resistant bacteria such as Staphylococcus aureus, Escherichia coli, Vibrio cholera and Pseudomonas aeruginosa (19, 28–30). The studies on silver-doped titania nanoparticles showed that this particles exhibits high activity against Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and E. coli bacteria (31, 32). It has been mentioned that SNPs have antimicrobial activities against antibiotic resistant bacteria, without conveying the formation of resistances that is one of the challenging problems with using antibiotics (33–35). However, it has to be indicated that the formation of resistances to NPs were identified and there might be a concern about increasing resistance of microorganisms against SNPs in the future (36, 37).

Wound dressings SNPs, are available in markets and relatively safe for human health (11). Silver is also used on medical devices which implanted in the body for long periods of time (38, 39). Currently, it has been used on dental materials (40). The antimicrobial activity of SNPs against the oral pathogenic species, Streptococcus mutans was investigated and the results were compared to a dental disinfectant, chlorhexidine. The results proved that SNPs are more efficient than chlorhexidine (41). SNPs also are employed for other purposes such as water purification and biosensors (42, 43). Most importantly, the antimicrobial activity of SNPs has been mainly occurred in one and pure microorganism and it seems that such kind of studies to show the impact of SNPs on complex microbial communities are needed.

Overview of SNPs toxicity

Nowadays, along with the rapid progress and development of NPs, is necessary to have guidelines and regulations to reduce the potential risk associated with the use and application of NPs on human health and the environment. As recommended by experts the safety data sheets for all NPs has to be prepared unless, the toxicity tests required by the regulatory entities to show that they are not toxic for human. In particular, only limited health effects of SNPs in humans have been documented so far and less is known about their environmental impacts (44, 45). It is plausible that SNPs can release into the aquatic environment, affect on the aquatic biota (46, 47) and possibly circulate in the food chain. For instance, it has been reported that SNPs have a developmental impact on the zebrafish embryos (Danio rerio) (48–51). Occupational studies are relatively limited and in a few studies, workers have been exposed to low levels of SNPs under the threshold limit values and for a short period of time (52–54). Thus, to fill this knowledge gap reliable epidemiological and eco-toxicological studies are required. Toxicity of SNPs are linked with several physicochemical properties such as size, the chemical nature, surface area, reactivity and charge, compositions and ease of aggregations. It is believed that small particles are more toxic than larger particles but, the particle size is not the only factor that determines NPs toxicity (55–58). The size-dependent toxicity of SNPs has been tested in vitro and in vivo. In both models, smaller SNPs exhibited more toxicity than large particles (59–61). The surface coating is another important issue that contributes to the NPs toxicity. Several physicochemical properties such as surface charge, differential binding and aggregation potential can be influenced by the surface coatings of silver nanoparticles. It seems that some uncoated SNPs are less toxic than coated SNPs (62). Current literature demonstrates the importance of releasing silver ions and its contribution to the NPs toxicity. However, this hypothesis not yet completely accepted (63). It seems that the acute toxicity of silver and silver related compounds is due to the released silver ions (49, 64), therefore the critical impact of exposure media on the SNPs toxicity has to be taken in consideration. High concentrations of chloride ions (Cl) can cause precipitation of silver ion in the media as reported in the performed experiments on zebrafish and fish gill cell line (64, 65). The authors then concluded that the levels of free Ag+ in the absence of chelators would be much higher and consequently SNPs toxicity would be augmented (65). From another side of view, chelators may directly neutralize the ROS and ameliorate SNPs toxicity (66).

Human exposures to silver and silver-related compounds mainly take place through three different routes of exposure, including dermal, oral and inhalation and subsequently, SNPs accumulate within secondary organ targets including liver, spleen and brain (67). As a matter of fact, prediction of SNPs toxicity is largely influenced by volume of distribution in the body (68). There is a gender-related difference in the distribution and kinetic profile of SNPs in mice (69). It has been shown that oral or intravenous administration of SNPs can cause gradual accumulation in the kidneys and brain (70, 71) and excretion from the body via feces and urine (72). SNPs after interring biological systems may undergoes biochemical transformation leading to the formation of secondary particles and this may lead to long harmful effects on human health (73–76). However, in long-term exposure, liver and spleen are the major site of SNPs accumulation and toxicity (Table 1). Finally, systemic argyria as the most prominent human clinical feature of colloidal silver ingestion has been reported (77).

Table 1

In vitro and in vivo toxicity of SNPs.

Skin toxicity

It has been shown that SNPs in wound dressing, medical applications promote rapid wound healing of pig’s wounds (78, 79). The proteolysis environment of the wounds treated with SNPs is characterized by reduced levels of metalloproteinase and enhanced cellular apoptosis. The skin absorption of SNPs was evaluated in vitro and in vivo. The results showed that the skin absorption of SNPs is low but, detectable (80–82). In our sub-chronic study, SNPs were locally applied on the back of guinea pigs once daily for 5 days per week over a period of 13 weeks. A close correlation between dermal exposure and tissue accumulations of SNPs were monitored (83) using transmission electron microscopy (TEM) and X-ray diffraction (XRD). Indeed, a time-course and dose-dependent effects of SNPs on the skin were seen. Moreover, decreasing dermis and epidermis thickness were along with the increased number of Langerhans cells, increased inflammation markers, decreased thickness of papillary layers, and increased dermis collagen levels (84).

Clinical safety data sheet of SNPs-based dressings are to some extent questionable (85, 86). It seems that nanocrystalline coated dressings are the most toxic SNPs-based dressings (86, 87). Acticoat® formula has been tested in a small clinical trial study and contradictory results have been reported (88). In a porcine model of wound healing, SNPs wound dressing promoted rapid wound healing (78) with no side effects. The potential cytotoxicity of SNPs in human epidermal keratinocytes (in vitro study) and penetrating ability in porcine skin has been assessed (in vivo study) by Samberg et al. (82). The authors used eight different types of SNPs and skin has been topically exposed for 2 weeks. The results have shown that SNPs were nontoxic when applied purely (82). The authors concluded that the toxicity of SNPs in human epidermal keratinocytes can be influenced by the residual contaminants in the solutions, and that the particles themselves may not have been responsible for increased cell death. In our studies during the acute test, dose-dependent histopathological abnormalities were seen in the skin. In addition, experimental animals that subjected to sub-chronic exposure, showed greater tissue abnormalities than the animals treated with single doses. It seems that colloidal solutions of SNPs have the potential ability to induce multi-organ toxicity in a dose- and time-dependent manner (84). Taken together, a clear correlation between dermal exposures, accumulation of SNPs and dose-dependent histopathological abnormalities in skin were found (Table 1).

Lung toxicity

In vitro studies revealed that different types of SNPs in a dose-dependent manner exhibited toxicity towards lung cell lines (62). The expression of gap junctional intercellular communication (GJIC) and connexin43 (Cx43) were increased in human lung adenocarcinoma cell line A549 and author suggested that Cx43 and GJIC may the targets of SNPs induce lung toxicity (89). In an in vivo study conducted in male and female rats lung function was evaluated and the results indicated that female rats were able to gradually recover from the lung inflammation, whereas the male rats in the high-dose group exhibited persistent inflammation throughout the 12-week recovery period (90). Acute and sub-acute exposures to SNPs induce mild pulmonary fibrosis and inflammation and persistent release of SNPs can lead to sub-chronic injury responses (58, 91, 92). Animal studies revealed that oxidative stress is involved in this process, triggering lung tissue damages (93). One of the most important factors that can affect on the SNPs lung toxicity is the rate of intracellular Ag ion release (94). The studies conducted with different size of SNPs have indicated that smaller SNPs (10 nm) is more toxic particles in human lung cells than larger SNPs (58, 95). Taken together, several factors can influence SNPs lung toxicity, including bioavailability, size, and surface of the coating as well as period of exposure (Table 1).

Gastrointestinal toxicity

Since, the gastrointestinal system represents an important route of entry of SNPs into the human body either directly through intentional ingestion or trough systemic circulation, the fate of SNPs after entering the gastrointestinal system is not yet known. It has been shown that oral administration of SNPs exhibit toxic effects (96, 97). In one study, a dose-dependent increased accumulation of SNPs in the lamina propria in both the small and large intestine, in the tip of the upper villi, the ileum and the protruding surface of the colon has been reported (98). In another animal study, SNPs were labeled with the silver radioactive isotope and administered intra-gastrically to pregnant female rats. Then the accumulation of SNPs in the rat fetuses was evaluated. The data demonstrated that SNPs can be penetrated through the placenta into the fetus body and accumulate in the fetus’s liver, blood, brain and muscles (99). Penetration of SNPs from the intestinal loop to the other organs has been also reported (100). It is clear that SNPs are able to penetrate from the gastrointestinal tract into the human body and accumulating in the other organs (Table 1) to prove the local and systemic effects of SNPs on gastrointestinal system more human and experimental data are required.

Liver toxicity

In vitro study with human liver C3A cell line revealed that SNPs elicited the maximum level of cytotoxicity [half maximal inhibitory concentration of 2 μg/cm(2)] (101). Liver is a main target organ of chemical detoxification and toxicity (Table 1). It has been shown that SNPs can be accumulated in the liver after inhalation exposure (102). Liver biomarkers such as aspartate amino transferase (AST), alanine aminotransferase (ALT) and gamma-galactosyltransferase and histopathological parameters after SNPs administration were elevated (103). In accordance, the activities of several cytochrome P450 (CYP) enzymes such as CYP1A, CYP2C, CYP2D, CYP2E1 and CYP3A were inhibited by SNPs exposure (104, 105). It seems that SNPs are able to induce oxidative stress and cause cell damage and apoptosis in human liver cells trough different mechanisms (106–108). Cytoplasmic vacuolization and hepatic focal necrosis were seen after SNPs exposure (109). In our study, necrosis were observed only at the highest SNPs concentrations (10,000 μg/mL) (84). Toxic concentrations of SNPs are linked with induction of apoptosis and increased micronucleus formation and chromosomal damage (110).

Kidney toxicity

As the kidneys are the major organ of drug elimination, at the same way they might be potential targets of SNPs toxicity (Table 1). SNPs can be accumulated in the kidneys in a dose-dependent manner as reported by Kim and co-workers (111). Some medical devices that are loaded with SNPs can release silver ions (Ag+) gradually, and then it can translocate into the blood circulation and accumulate in the kidneys (112). In response to SNPs exposure, proximal convoluted tubule degeneration, capsular and membranous thickening and mesangial abnormality have been reported (111). In our study, a clear relationship between dermal exposure and accumulation of SNPs in the kidneys was observed. After evaluation of 28 kidneys of treated animals and comparing the levels with the control group, six major toxic responses were recorded. Histopathological data showed inflammation, adhesion to Bowman’s capsule, proximal convoluted tubule degeneration, capsular thickening, membranous thickening and increased mesangial cells in SNPs treated animals (83). It seems that more cautions and special attention have to be devoted to long-term using of SNPs in medical applications.

Muscle toxicity

In an occupational study, a group of workers was exposed to silver compounds. During experiments, an increasing in the N-acetyl-B-D glucoseaminidase (NAG) level and decreasing in the creatinine clearance has been observed (113). In our dermal study, the histopathological data confirm the toxic effects of SNPs on muscles (83). It seems that colloidal SNPs have the ability to create a dose-dependent toxic response in this organ. We found that both small and large sizes of SNPs were able to distribute in the muscles and induce muscle toxicity using transmission electron microscopy (TEM) and X-ray diffraction (XRD) (83). In agreement with us, muscular effects of SNPs have been reported in the other studies (114, 115).

Nervous system toxicity

Accordingly, the role of glutamatergic N-methyl-d-aspartate receptor (NMDA) in SNPs-evoked neurotoxicity has been investigated and the authors concluded that activation of NMDA is involved in the SNPs neurotoxicity (116). It was also documented that SNPs can cross the BBB and induces brain inflammation and neurotoxicity (117). It has been also reported that silver can be found within the BBB but could not pass through it (118). However, in vitro studies demonstrated that SNPs are toxic to brain cells (119). High levels of silver in plasma, erythrocytes and cerebro-spinal fluid along with epileptic seizures and coma after daily ingestion of colloidal silver have been reported (120). This study also suggested that silver exposure can induce irreversible neurotoxicity which, eventually can lead to death. In contrary, no remarkable symptoms in the brain of rats that was exposed to SNPs via inhalation has been seen in another study (102, 109). Taken together, the current knowledge about central nervous system effects of SNPs are extremely limited and more clinical and experimental data are needed (Table 1).

Reproductive and developmental toxicity

The potential harmful effects of NPs on pregnant women and fetuses development are an important issue that has to be included in SNPs safety data sheets. The impact of SNPs on the proper functions of reproductive system has been tested in several studies (121, 122) (Table 1). The male fertility can be affected by NPs because spermatogenesis is very sensitive to these chemicals. The impact of dose, size and coating of SNPs to stimulate mouse spermatogonial stem cell proliferation was evaluated. According to in vitro studies, mouse spermatogonial stem cell viability was reduced in a size- and dose-dependent manner while SNPs coating had no effect on cell growth (122, 123). In one short term in vivo study, male CD1 mice were subjected to low concentrations of SNPs intravenously for 12 days. The data suggest that SNPs are not able to significantly reduce testis weight and sperm numbers but, it can alter the leydig cellular functions that lead to increase in the testicular and serum testosterone levels (124). In contrast, SNPs inhalation exposure has been shown to have no effect on the histopathology of the epididymis (109). Especially after inhalation exposure the systemic availability of NPs may be limited. In one study performed on pregnant CD-1 mice, SNPs intravenously administrated and after gestation days tissue samples were collected to evaluate silver content in different organs. The results demonstrated that SNPs were significantly accumulated in the visceral yolk sac and endometrium (125). In another study, reproductive and developmental toxicity of SNPs in both male and female rats has been investigated. No remarkable signs of reproductive and developmental toxicity in this study were reported (126) whereas, in zebrafish SNPs were distributed in the brain, heart, yolk and blood of embryos and induced several developmental abnormalities that restrict the survival chances of zebrafish embryos (48, 49). Taken together, there are insufficient information and limited acceptable studies on the reproductive and developmental toxicity of SNPs (Table 1).

Immune system toxicity

The in vivo nano-immune interaction studies are extremely limited and more caution is needed when NPs prescribed in biomedical applications. SNPs have been shown to be accumulated in the spleen of rats after inhalation exposure (102). A close correlation between dermal exposure and spleen accumulation was found in our study (83). The presence of SNPs at high concentrations in the respiratory system that was connected with local inflammatory responses has been reported. Systemic immune effects of SNPs have also been reported (127). SNPs larger than 100 nm can be readily phagocytized by alveolar macrophages (102, 128, 129) but smaller SNPs (<100 nm) tend to aggregate and inhibit alveolar macrophage activities (102). Thus, the smaller particles may be effective to treat inflammatory diseases (130). Further studies are necessary to determine whether high doses of SNPs can inhibit local inflammatory responses or not (92). However, application of SNPs in wound dressing formula could stimulate the immune system with no adverse effects (131). According to our results, SNPs can induce spleen toxicity. In animals that received low and medium concentrations of SNPs several signs of inflammation were observed (84) (Table 1).

Genotoxicity and carcinogenicity

The genotoxic effects of SNPs on calf thymus DNA have been reported. The results demonstrated that SNPs interaction with detergent induced genotoxicity (132). SNPs were able to interfere with the replication of DNA molecules and cause mutations (133) and to induce genotoxic activity in Drosophila (134). With subcutaneous administration, but not through intramuscular injection, tumor formation at the site of application has been observed (135–137). Toxic concentrations of SNPs are linked with the increased micronucleus formation and chromosomal damage (110). The in vivo administration of 60 nm SNP for 28 days has been conducted, but no statistically considerable genotoxic effects were seen (111). In an in vitro study, bulky DNA adducts and micronuclei formations in human cell lines were seen (138, 139). Interestingly, SNPs are more toxic to cancerous cells (140, 141) than normal cells and this may be valuable for developing anticancer drugs in the future studies. In this respect, human and animal studies are considerably limited and further studies are required to draw final conclusions. In conclusion, there is inadequate evidence in humans for the carcinogenicity of SNPs, but there is limited evidence in experimental animals and in vitro studies.

Conclusion

SNPs have become one of the most frequently used NPs because of their potential antibacterial activities (85, 108, 142). In addition to binding affinity, several parameters such as size and surface area are recognized as important determinants of SNPs toxicity (55, 56). First of all, SNPs have to pass through the biological membranes. It seems that SNPs are small enough to penetrate through body barriers (143). Human exposure to silver and silver-related compounds mainly takes place through three different routes of exposure, including skin, gastrointestinal and lung. After absorption SNPs can be distributed in the blood and brain, and subsequently, to the other organs, such as heart and kidney. Smaller SNPs tend to be aggregated and inhibit the immune system, therefore their accumulation in the spleen may especially be effective in treating inflammatory diseases. Research on SNPs toxicity is mostly conducted in vitro with particles ranging from 1 to 100 nm. The available animal studies are relatively short term studies. On the other hand, research about the effect of SNPs on human health is limited. Sub-chronic dermal exposure can cause considerable accumulation of SNPs in the liver and lung (144). Animal available data have shown that SNPs causes histopathologic abnormalities in spleen, liver and skin (83). Our result clearly showed that muscles also are target organs of SNPs toxicity (144). It seems that colloidal SNPs have the ability to create a dose-dependent toxic response in several organs. In conclusion, there are very limited well controlled human studies on the potential toxicities of SNPs and further long term, wide range doses, preferably using multiple particle sizes, are needed to better characterize the risk of SNPs on human health. It is highly recommended to detect the role of shape and particle size on the toxicity profile of SNPs by different routes of administration in the future studies.

Acknowledgments

This work was supported by the Tehran University of Medical Sciences.

References

  • 1.

    Kim HS, Ryu JH, Jose B, Lee BG, Ahn BS, Kang YS. Formation of silver nanoparticles induced by poly(2,6-dimethyl-1,4-phenylene oxide). Langmuir 2001;17:5817–20.CrossrefGoogle Scholar

  • 2.

    Besinis A, De Peralta T, Handy RD. Inhibition of biofilm formation and antibacterial properties of a silver nano-coating on human dentine. Nanotoxicology 2014;8:745–54.Google Scholar

  • 3.

    Panigrahi S, Kundu S, Ghosh S, Nath S, Pal T. General method of synthesis for metal nanoparticles. J Nanopart Res 2004;6:411–4.CrossrefGoogle Scholar

  • 4.

    Bansal V, Bharde A, Ramanathan R, Bhargava SK. Inorganic materials using ‘unusual’ microorganisms. Adv Colloid Interface Sci 2012;179–182:150–68.Google Scholar

  • 5.

    Bai HJ, Yang BS, Chai CJ, Yang GE, Jia WL, Yi ZB. Green synthesis of silver nanoparticles using Rhodobacter Sphaeroides. World J Microb Biotech 2011;27:2723–8.CrossrefGoogle Scholar

  • 6.

    Kumar CG, Mamidyala SK. Extracellular synthesis of silver nanoparticles using culture supernatant of Pseudomonas aeruginosa. Colloids Surf B Biointerfaces 2011;84:462–6.CrossrefGoogle Scholar

  • 7.

    Soni N, Prakash S. Fungal-mediated nano silver: an effective adulticide against mosquito. Parasitol Res 2012;111:2091–8.CrossrefGoogle Scholar

  • 8.

    Barwal I, Ranjan P, Kateriya S, Yadav SC. Cellular oxido-reductive proteins of Chlamydomonas reinhardtii control the biosynthesis of silver nanoparticles. J Nanobiotechnology 2011;9:56.Google Scholar

  • 9.

    Antony JJ, Sivalingam P, Siva D, Kamalakkannan S, Anbarasu K, Sukirtha R, et al. Comparative evaluation of antibacterial activity of silver nanoparticles synthesized using Rhizophora apiculata and glucose. Colloids Surf B Biointerfaces 2011;88:134–40.CrossrefGoogle Scholar

  • 10.

    Fayaz AM, Girilal M, Venkatesan R, Kalaichelvan PT. Biosynthesis of anisotropic gold nanoparticles using Maduca longifolia extract and their potential in infrared absorption. Colloids Surf B Biointerfaces 2011;88:287–91.CrossrefGoogle Scholar

  • 11.

    Wilkinson LJ, White RJ, Chipman JK. Silver and nanoparticles of silver in wound dressings: a review of efficacy and safety. J Wound Care 2011;20:543–9.CrossrefGoogle Scholar

  • 12.

    Edwards-Jones V. The benefits of silver in hygiene, personal care and healthcare. Lett Appl Microbiol 2009;49:147–52.CrossrefGoogle Scholar

  • 13.

    Hebeish A, El-Rafie MH, El-Sheikh MA, Seleem AA, El-Naggar ME. Antimicrobial wound dressing and anti-inflammatory efficacy of silver nanoparticles. Int J Biol Macromol 2014;65:509–15.CrossrefGoogle Scholar

  • 14.

    Kim JS, Kuk E, Yu KN, Kim JH, Park SJ, Lee HJ, et al. Antimicrobial effects of silver nanoparticles. Nanomedicine 2007;3:95–101.Google Scholar

  • 15.

    Chernousova S, Epple M. Silver as antibacterial agent: ion, nanoparticle, and metal. Angew Chem Int Ed Engl 2013;52:1636–53.CrossrefGoogle Scholar

  • 16.

    Yu H, Xu X, Chen X, Lu T, Zhang P. Preparation and antibacterial effects of PVA-PVP hydrogels containing silver nanoparticles. Journal of Applied Polymer Science 2007;103:125–33.CrossrefGoogle Scholar

  • 17.

    Jin X, Li M, Wang J, Marambio-Jones C, Peng F, Huang X, et al. High-throughput screening of silver nanoparticle stability and bacterial inactivation in aquatic media: influence of specific ions. Environ Sci Technol 2010;44:7321–8.CrossrefGoogle Scholar

  • 18.

    Musee N, Thwala M, Nota N. The antibacterial effects of engineered nanomaterials: implications for wastewater treatment plants. J Environ Monit 2011;13:1164–83.CrossrefGoogle Scholar

  • 19.

    Morones JR, Elechiguerra JL, Camacho A, Holt K, Kouri JB, Ramírez JT, et al. The bactericidal effect of silver nanoparticles. Nanotechnology 2005;16:2346–53.CrossrefGoogle Scholar

  • 20.

    Sibbald RG, Contreras-Ruiz J, Coutts P, Fierheller M, Rothman A, Woo K. Bacteriology, inflammation, and healing: a study of nanocrystalline silver dressings in chronic venous leg ulcers. Adv Skin Wound Care 2007;20:549–58.Google Scholar

  • 21.

    Lamsal K, Kim SW, Jung JH, Kim YS, Kim KS, Lee YS. Application of silver nanoparticles for the control of colletotrichum species in vitro and pepper anthracnose disease in field. Mycobiology 2011;39:194–9.CrossrefGoogle Scholar

  • 22.

    Hwang IS, Lee J, Hwang JH, Kim KJ, Lee DG. Silver nanoparticles induce apoptotic cell death in Candida albicans through the increase of hydroxyl radicals. FEBS J 2012;279:1327–38.CrossrefGoogle Scholar

  • 23.

    Kim SW, Jung JH, Lamsal K, Kim YS, Min JS, Lee YS. Antifungal Effects of Silver Nanoparticles (AgNPs) against Various Plant Pathogenic Fungi. Mycobiology 2012;40:53–8.CrossrefGoogle Scholar

  • 24.

    Nam KY, Lee CH, Lee CJ. Antifungal and physical characteristics of modified denture base acrylic incorporated with silver nanoparticles. Gerodontology 2012;29:e413–9.CrossrefGoogle Scholar

  • 25.

    Zodrow K, Brunet L, Mahendra S, Li D, Zhang A, Li Q, et al. Polysulfone ultrafiltration membranes impregnated with silver nanoparticles show improved biofouling resistance and virus removal. Water Res 2009;43:715–23.CrossrefGoogle Scholar

  • 26.

    Salunkhe RB, Patil SV, Patil CD, Salunke BK. Larvicidal potential of silver nanoparticles synthesized using fungus Cochliobolus lunatus against Aedes aegypti (Linnaeus, 1762) and Anopheles stephensi Liston (Diptera; Culicidae). Parasitol Res 2011;109:823–31.Google Scholar

  • 27.

    Silver S. Bacterial silver resistance: molecular biology and uses and misuses of silver compounds. FEMS Microbiol Rev 2003;27:341–53.CrossrefGoogle Scholar

  • 28.

    Mukha Iu P, Eremenko AM, Smirnova NP, Mikhienkova AI, Korchak GI, Gorchev VF, et al. Antimicrobial activity of stable silver nanoparticles of a certain size. Prikl Biokhim Mikrobiol 2013;49:215–23.Google Scholar

  • 29.

    Pokrowiecki R, Zareba T, Mielczarek A, Opalińska A, Wojnarowicz J, Majkowski M, et al. Evaluation of biocidal properties of silver nanoparticles against cariogenic bacteria. Med Dosw Mikrobiol 2013;65:197–206.Google Scholar

  • 30.

    Priester JH, Singhal A, Wu B, Stucky GD, Holden PA. Integrated approach to evaluating the toxicity of novel cysteine-capped silver nanoparticles to Escherichia coli and Pseudomonas aeruginosa. Analyst 2014;139:954–63.CrossrefGoogle Scholar

  • 31.

    Shahverdi AR, Fakhimi A, Shahverdi HR, Minaian S. Synthesis and effect of silver nanoparticles on the antibacterial activity of different antibiotics against Staphylococcus aureus and Escherichia coli. Nanomedicine 2007;3:168–71.Google Scholar

  • 32.

    Thiel J, Pakstis L, Buzby S, Raffi M, Ni C, Pochan DJ, et al. Antibacterial properties of silver-doped titania. Small 2007;3:799–803.CrossrefGoogle Scholar

  • 33.

    Naqvi SZ, Kiran U, Ali MI, Jamal A, Hameed A, Ahmed S, et al. Combined efficacy of biologically synthesized silver nanoparticles and different antibiotics against multidrug-resistant bacteria. Int J Nanomedicine 2013;8:3187–95.CrossrefGoogle Scholar

  • 34.

    Miller JH, Novak JT, Knocke WR, Young K, Hong Y, Vikesland PJ, et al. Effect of silver nanoparticles and antibiotics on antibiotic resistance genes in anaerobic digestion. Water Environ Res 2013;85:411–21.CrossrefGoogle Scholar

  • 35.

    Prakash P, Gnanaprakasam P, Emmanuel R, Arokiyaraj S, Saravanan M. Green synthesis of silver nanoparticles from leaf extract of Mimusops elengi, Linn. for enhanced antibacterial activity against multi drug resistant clinical isolates. Colloids Surf B Biointerfaces 2013;108:255–9.CrossrefGoogle Scholar

  • 36.

    Mijnendonckx K, Leys N, Mahillon J, Silver S, Van Houdt R. Antimicrobial silver: uses, toxicity and potential for resistance. Biometals 2013;26:609–21.CrossrefGoogle Scholar

  • 37.

    Maillard JY, Hartemann P. Silver as an antimicrobial: facts and gaps in knowledge. Crit Rev Microbiol 2013;39:373–83.CrossrefGoogle Scholar

  • 38.

    Taheri S, Cavallaro A, Christo SN, Smith LE, Majewski P, Barton M, et al. Substrate independent silver nanoparticle based antibacterial coatings. Biomaterials 2014;35:4601–9.CrossrefGoogle Scholar

  • 39.

    Cheng H, Li Y, Huo K, Gao B, Xiong W. Long-lasting in vivo and in vitro antibacterial ability of nanostructured titania coating incorporated with silver nanoparticles. J Biomed Mater Res A 2014;102:3488–99.CrossrefGoogle Scholar

  • 40.

    Liao J, Anchun M, Zhu Z, Quan Y. Antibacterial titanium plate deposited by silver nanoparticles exhibits cell compatibility. Int J Nanomedicine 2010;5:337–42.Google Scholar

  • 41.

    Besinis A, De Peralta T, Handy RD. The antibacterial effects of silver, titanium dioxide and silica dioxide nanoparticles compared to the dental disinfectant chlorhexidine on Streptococcus mutans using a suite of bioassays. Nanotoxicology 2014;8:1–16.CrossrefGoogle Scholar

  • 42.

    Zhang YY, Sun J. A study on the bio-safety for nano-silver as anti-bacterial materials. Zhongguo Yi Liao Qi Xie Za Zhi 2007;31:36–8, 16.Google Scholar

  • 43.

    Wang GL, Xu XF, Qiu L, Dong YM, Li ZJ, Zhang C. Dual responsive enzyme mimicking activity of AgX (X = Cl, Br, I) nanoparticles and its application for cancer cell detection. ACS Appl Mater Interfaces 2014;6:6434–42.CrossrefGoogle Scholar

  • 44.

    Kuhnel D, Nickel C. The OECD expert meeting on ecotoxicology and environmental fate – towards the development of improved OECD guidelines for the testing of nanomaterials. Sci Total Environ 2014;472:347–53.CrossrefGoogle Scholar

  • 45.

    Lowry GV, Hotze EM, Bernhardt ES, Dionysiou DD, Pedersen JA, Wiesner MR, et al. Environmental occurrences, behavior, fate, and ecological effects of nanomaterials: an introduction to the special series. J Environ Qual 2010;39:1867–74.CrossrefGoogle Scholar

  • 46.

    Kaegi R, Sinnet B, Zuleeg S, Hagendorfer H, Mueller E, Vonbank R, et al. Release of silver nanoparticles from outdoor facades. Environ Pollut 2010;158:2900–5.CrossrefGoogle Scholar

  • 47.

    Blaser SA, Scheringer M, Macleod M, Hungerbuhler K. Estimation of cumulative aquatic exposure and risk due to silver: contribution of nano-functionalized plastics and textiles. Sci Total Environ 2008;390:396–409.CrossrefGoogle Scholar

  • 48.

    Asharani PV, Lian Wu Y, Gong Z, Valiyaveettil S. Toxicity of silver nanoparticles in zebrafish models. Nanotechnology 2008;19:255102.CrossrefGoogle Scholar

  • 49.

    Osborne OJ, Johnston BD, Moger J, Balousha M, Lead JR, Kudoh T, et al. Effects of particle size and coating on nanoscale Ag and TiO(2) exposure in zebrafish (Danio rerio) embryos. Nanotoxicology 2013;7:1315–24.CrossrefGoogle Scholar

  • 50.

    van Aerle R, Lange A, Moorhouse A, Paszkiewicz K, Ball K, Johnston BD, et al. Molecular mechanisms of toxicity of silver nanoparticles in zebrafish embryos. Environ Sci Technol 2013;47:8005–14.CrossrefGoogle Scholar

  • 51.

    Lee KJ, Nallathamby PD, Browning LM, Osgood CJ, Xu XH. In vivo imaging of transport and biocompatibility of single silver nanoparticles in early development of zebrafish embryos. ACS Nano 2007;1:133–43.CrossrefGoogle Scholar

  • 52.

    Lee JH, Mun J, Park JD, Yu IJ. A health surveillance case study on workers who manufacture silver nanomaterials. Nanotoxicology 2012;6:667–9.CrossrefGoogle Scholar

  • 53.

    Drake PL, Hazelwood KJ. Exposure-related health effects of silver and silver compounds: a review. Ann Occup Hyg 2005;49:575–85.CrossrefGoogle Scholar

  • 54.

    Lamberti M, Zappavigna S, Sannolo N, Porto S, Caraglia M. Advantages and risks of nanotechnologies in cancer patients and occupationally exposed workers. Expert Opin Drug Deliv 2014;11:1087–101.CrossrefGoogle Scholar

  • 55.

    Brown DM, Wilson MR, MacNee W, Stone V, Donaldson K. Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicol Appl Pharmacol 2001;175:191–9.CrossrefGoogle Scholar

  • 56.

    Duffin R, Tran L, Brown D, Stone V, Donaldson K. Proinflammogenic effects of low-toxicity and metal nanoparticles in vivo and in vitro: highlighting the role of particle surface area and surface reactivity. Inhal Toxicol 2007;19:849–56.CrossrefGoogle Scholar

  • 57.

    Xiong Y, Brunson M, Huh J, Huang A, Coster A, Wendt K, et al. The role of surface chemistry on the toxicity of Ag nanoparticles. Small 2013;9:2628–38.CrossrefGoogle Scholar

  • 58.

    Wang X, Ji Z, Chang CH, Zhang H, Wang M, Wang M, et al. Use of coated silver nanoparticles to understand the relationship of particle dissolution and bioavailability to cell and lung toxicological potential. Small 2014;10:385–98.CrossrefGoogle Scholar

  • 59.

    Georgantzopoulou A, Balachandran YL, Rosenkranz P, Dusinska M, Lankoff A, Wojewodzka M, et al. Ag nanoparticles: size- and surface-dependent effects on model aquatic organisms and uptake evaluation with NanoSIMS. Nanotoxicology 2013;7:1168–78.Google Scholar

  • 60.

    Liu W, Wu Y, Wang C, Li HC, Wang T, Liao CY, et al. Impact of silver nanoparticles on human cells: effect of particle size. Nanotoxicology 2010;4:319–30.CrossrefGoogle Scholar

  • 61.

    Pratsinis A, Hervella P, Leroux JC, Pratsinis SE, Sotiriou GA. Toxicity of silver nanoparticles in macrophages. Small 2013;9:2576–84.CrossrefGoogle Scholar

  • 62.

    Suresh AK, Pelletier DA, Wang W, Morrell-Falvey JL, Gu B, Doktycz MJ. Cytotoxicity induced by engineered silver nanocrystallites is dependent on surface coatings and cell types. Langmuir 2012;28:2727–35.CrossrefGoogle Scholar

  • 63.

    Maurer EI, Sharma M, Schlager JJ, Hussain SM. Systematic analysis of silver nanoparticle ionic dissolution by tangential flow filtration: toxicological implications. Nanotoxicology 2014;8:718–27.Google Scholar

  • 64.

    Yue Y, Behra R, Sigg L, Fernandez Freire P, Pillai S, Schirmer K. Toxicity of silver nanoparticles to a fish gill cell line: role of medium composition. Nanotoxicology 2014.Google Scholar

  • 65.

    Groh KJ, Dalkvist T, Piccapietra F, Behra R, Suter MJ, Schirmer K. Critical influence of chloride ions on silver ion-mediated acute toxicity of silver nanoparticles to zebrafish embryos. Nanotoxicology 2013.Google Scholar

  • 66.

    Jiang X, Miclaus T, Wang L, Foldbjerg R, Sutherland DS, Autrup H, et al. Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity. Nanotoxicology 2014.Google Scholar

  • 67.

    Lankveld DP, Oomen AG, Krystek P, Neigh A, Troost-de Jong A, Noorlander CW, et al. The kinetics of the tissue distribution of silver nanoparticles of different sizes. Biomaterials. Biomaterials 2010;31:8350–61.CrossrefGoogle Scholar

  • 68.

    Seaton A, Tran L, Aitken R, Donaldson K. Nanoparticles, human health hazard and regulation. J R Soc Interface 2009;7(Suppl 1):S119–29.Google Scholar

  • 69.

    Xue Y, Zhang S, Huang Y, Zhang T, Liu X, Hu Y, et al. Acute toxic effects and gender-related biokinetics of silver nanoparticles following an intravenous injection in mice. J Appl Toxicol 2012;32:890–9.CrossrefGoogle Scholar

  • 70.

    Dziendzikowska K, Gromadzka-Ostrowska J, Lankoff A, Oczkowski M, Krawczyńska A, Chwastowska J, et al. Time-dependent biodistribution and excretion of silver nanoparticles in male Wistar rats. J Appl Toxicol 2012;32:920–8.CrossrefGoogle Scholar

  • 71.

    Park K, Park EJ, Chun IK, Choi K, Lee SH, Yoon J, et al. Bioavailability and toxicokinetics of citrate-coated silver nanoparticles in rats. Arch Pharm Res 2011;34:153–8.CrossrefGoogle Scholar

  • 72.

    Lee Y, Kim P, Yoon J, Lee B, Choi K, Kil KH, et al. Serum kinetics, distribution and excretion of silver in rabbits following 28 days after a single intravenous injection of silver nanoparticles. Nanotoxicology 2013;7:1120–30.Google Scholar

  • 73.

    Liu J, Wang Z, Liu FD, Kane AB, Hurt RH. Chemical transformations of nanosilver in biological environments. ACS Nano 2012;6:9887–99.CrossrefGoogle Scholar

  • 74.

    Lowry GV, Espinasse BP, Badireddy AR, Richardson CJ, Reinsch BC, Bryant LD, et al. Long-term transformation and fate of manufactured Ag nanoparticles in a simulated large scale freshwater emergent wetland. Environ Sci Technol 2012;46:7027–36.CrossrefGoogle Scholar

  • 75.

    Liu J, Pennell KG, Hurt RH. Kinetics and mechanisms of nanosilver oxysulfidation. Environ Sci Technol 2011;45:7345–53.CrossrefGoogle Scholar

  • 76.

    Khan SS, Srivatsan P, Vaishnavi N, Mukherjee A, Chandrasekaran N. Interaction of silver nanoparticles (SNPs) with bacterial extracellular proteins (ECPs) and its adsorption isotherms and kinetics. J Hazard Mater 2011;192:299–306.Google Scholar

  • 77.

    Wadhera A, Fung M. Systemic argyria associated with ingestion of colloidal silver. Dermatol Online J 2005;11:12.Google Scholar

  • 78.

    Wright JB, Lam K, Buret AG, Olson ME, Burrell RE. Early healing events in a porcine model of contaminated wounds: effects of nanocrystalline silver on matrix metalloproteinases, cell apoptosis, and healing. Wound Repair Regen 2002;10:141–51.CrossrefGoogle Scholar

  • 79.

    Lam PK, Chan ES, Ho WS, Liew CT. In vitro cytotoxicity testing of a nanocrystalline silver dressing (Acticoat) on cultured keratinocytes. Br J Biomed Sci 2004;61:125–7.CrossrefGoogle Scholar

  • 80.

    Filon FL, D’Agostin F, Crosera M, Adami G, Rosani R, Romano C, et al. In vitro percutaneous absorption of silver nanoparticles. G Ital Med Lav Ergon 2007;29:451–2.Google Scholar

  • 81.

    Larese FF, D’Agostin F, Crosera M, Adami G, Renzi N, Bovenzi M, et al. Human skin penetration of silver nanoparticles through intact and damaged skin. Toxicology 2009;255:33–7.Google Scholar

  • 82.

    Samberg ME, Oldenburg SJ, Monteiro-Riviere NA. Evaluation of silver nanoparticle toxicity in skin in vivo and keratinocytes in vitro. Environ Health Perspect 2010;118:407–13.Google Scholar

  • 83.

    Korani M, Rezayat SM, Arbabi Bidgoli S. Sub-chronic dermal toxicity of silver nanoparticles in guinea pig: special emphasis to heart, bone and kidney toxicities. Iran J Pharm Res 2013;12:511–9.Google Scholar

  • 84.

    Korani M, Rezayat SM, Gilani K, Arbabi Bidgoli S, Adeli S. Acute and subchronic dermal toxicity of nanosilver in guinea pig. Int J Nanomedicine 2011;6:855–62.CrossrefGoogle Scholar

  • 85.

    Chen X, Schluesener HJ. Nanosilver: a nanoproduct in medical application. Toxicol Lett 2008;176:1–12.CrossrefGoogle Scholar

  • 86.

    El-Ansary A, Al-Daihan S. On the toxicity of therapeutically used nanoparticles: an overview. J Toxicol 2009;2009:754810.Google Scholar

  • 87.

    Paddle-Ledinek JE, Nasa Z, Cleland HJ. Effect of different wound dressings on cell viability and proliferation. Plast Reconstr Surg 2006;117:110S–8S; discussion 9S–20S.CrossrefGoogle Scholar

  • 88.

    Tredget EE, Shankowsky HA, Groeneveld A, Burrell R. A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds. J Burn Care Rehabil 1998;19:531–7.CrossrefGoogle Scholar

  • 89.

    Deng F, Olesen P, Foldbjerg R, Dang DA, Guo X, Autrup H. Silver nanoparticles up-regulate Connexin43 expression and increase gap junctional intercellular communication in human lung adenocarcinoma cell line A549. Nanotoxicology 2010;4:186–95.Google Scholar

  • 90.

    Song KS, Sung JH, Ji JH, Lee JH, Lee JS, Ryu HR, et al. Recovery from silver-nanoparticle-exposure-induced lung inflammation and lung function changes in Sprague Dawley rats. Nanotoxicology 2013;7:169–80.CrossrefGoogle Scholar

  • 91.

    Stebounova LV, Adamcakova-Dodd A, Kim JS, Park H, O’Shaughnessy PT, Grassian VH, et al. Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model. Part Fibre Toxicol 2011;8:5.Google Scholar

  • 92.

    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;20:567–74.CrossrefGoogle Scholar

  • 93.

    Kaewamatawong T, Banlunara W, Maneewattanapinyo P, Thammachareon C, Ekgasit S. Acute and subacute pulmonary toxicity caused by a single intratracheal instillation of colloidal silver nanoparticles in mice: pathobiological changes and metallothionein responses. J Environ Pathol Toxicol Oncol 2014;33:59–68.CrossrefGoogle Scholar

  • 94.

    Leo BF, Chen S, Kyo Y, Herpoldt KL, Terrill NJ, Dunlop IE, et al. The stability of silver nanoparticles in a model of pulmonary surfactant. Environ Sci Technol 2013;47:11232–40.CrossrefGoogle Scholar

  • 95.

    Gliga AR, Skoglund S, Wallinder IO, Fadeel B, Karlsson HL. Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release. Part Fibre Toxicol 2014;11:11.Google Scholar

  • 96.

    van der Zande M, Vandebriel RJ, Van Doren E, Kramer E, Herrera Rivera Z, Serrano-Rojero CS, et al. Distribution, elimination, and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure. ACS Nano 2012;6:7427–42.CrossrefGoogle Scholar

  • 97.

    Hadrup N, Lam HR. Oral toxicity of silver ions, silver nanoparticles and colloidal silver–a review. Regul Toxicol Pharmacol 2013;68:1–7.Google Scholar

  • 98.

    Jeong GN, Jo UB, Ryu HY, Kim YS, Song KS, Yu IJ. Histochemical study of intestinal mucins after administration of silver nanoparticles in Sprague-Dawley rats. Arch Toxicol 2010;84:63–9.CrossrefGoogle Scholar

  • 99.

    Melnik EA, Buzulukov YP, Demin VF, Demin VA, Gmoshinski IV, Tyshko NV, et al. Transfer of silver nanoparticles through the placenta and breast milk during in vivo experiments on rats. Acta Naturae 2013;5:107–15.Google Scholar

  • 100.

    Platonova TA, Pridvorova SM, Zherdev AV, Vasilevskaya LS, Arianova EA, Gmoshinski IV, et al. Identification of silver nanoparticles in the small intestinal mucosa, liver, and spleen of rats by transmission electron microscopy. Bull Exp Biol Med 2013;155:236–41.CrossrefGoogle Scholar

  • 101.

    Kermanizadeh A, Pojana G, Gaiser BK, Birkedal R, Bilanicová D, Wallin H, et al. In vitro assessment of engineered nanomaterials using a hepatocyte cell line: cytotoxicity, pro-inflammatory cytokines and functional markers. Nanotoxicology 2013;7:301–13.Google Scholar

  • 102.

    Takenaka S, Karg E, Roth C, Schulz H, Ziesenis A, Heinzmann U, et al. Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. Environ Health Perspect 2001;109(Suppl 4):547–51.CrossrefGoogle Scholar

  • 103.

    Tiwari DK, Jin T, Behari J. Dose-dependent in-vivo toxicity assessment of silver nanoparticle in Wistar rats. Toxicol Mech Method 2011;21:13–24.CrossrefGoogle Scholar

  • 104.

    Kulthong K, Maniratanachote R, Kobayashi Y, Fukami T, Yokoi T. Effects of silver nanoparticles on rat hepatic cytochrome P450 enzyme activity. Xenobiotica 2012;42:854–62.Google Scholar

  • 105.

    Christen V, Fent K. Silica nanoparticles and silver-doped silica nanoparticles induce endoplasmatic reticulum stress response and alter cytochrome P4501A activity. Chemosphere 2012;87:423–34.CrossrefGoogle Scholar

  • 106.

    Piao MJ, Kang KA, Lee IK, Kim HS, Kim S, Choi JY, et al. Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. Toxicol Lett 2011;201:92–100.CrossrefGoogle Scholar

  • 107.

    Hsin YH, Chen CF, Huang S, Shih TS, Lai PS, Chueh PJ. The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. Toxicol Lett 2008;179:130–9.Google Scholar

  • 108.

    Kim S, Ryu DY. Silver nanoparticle-induced oxidative stress, genotoxicity and apoptosis in cultured cells and animal tissues. J Appl Toxicol 2013;33:78–89.CrossrefGoogle Scholar

  • 109.

    Ji JH, Jung JH, Kim SS, Yoon JU, Park JD, Choi BS, et al. Twenty-eight-day inhalation toxicity study of silver nanoparticles in Sprague-Dawley rats. Inhal Toxicol 2007;19:857–71.CrossrefGoogle Scholar

  • 110.

    Kawata K, Osawa M, Okabe S. In vitro toxicity of silver nanoparticles at noncytotoxic doses to HepG2 human hepatoma cells. Environ Sci Technol 2009;43:6046–51.Google Scholar

  • 111.

    Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, et al. Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats. Inhal Toxicol 2008;20:575–83.CrossrefGoogle Scholar

  • 112.

    Tang J, Xiong L, Wang S, Wang J, Liu L, Li J, et al. Distribution, translocation and accumulation of silver nanoparticles in rats. J Nanosci Nanotechnol 2009;9:4924–32.CrossrefGoogle Scholar

  • 113.

    Rosenman KD, Moss A, Kon S. Argyria: clinical implications of exposure to silver nitrate and silver oxide. J Occup Med 1979;21:430–5.Google Scholar

  • 114.

    Mahabady M. The evaluation of teratogenicity of nanosilver on skeletal system and placenta of rat fetuses in prenatal period. Afr J Pharm Pharmacol 2012;6:419–24.Google Scholar

  • 115.

    González C, Salazar-García S, Palestino G, Martínez-Cuevas PP, Ramírez-Lee MA, Jurado-Manzano BB, et al. Effect of 45 nm silver nanoparticles (AgNPs) upon the smooth muscle of rat trachea: role of nitric oxide. Toxicol Lett 2011;207:306–13.CrossrefGoogle Scholar

  • 116.

    Zieminska E, Stafiej A, Struzynska L. The role of the glutamatergic NMDA receptor in nanosilver-evoked neurotoxicity in primary cultures of cerebellar granule cells. Toxicology 2014;315:38–48.CrossrefGoogle Scholar

  • 117.

    Trickler WJ, Lantz SM, Murdock RC, Schrand AM, Robinson BL, Newport GD, et al. Silver nanoparticle induced blood-brain barrier inflammation and increased permeability in primary rat brain microvessel endothelial cells. Toxicol Sci 2010;118:160–70.CrossrefGoogle Scholar

  • 118.

    Lansdown AB. Critical observations on the neurotoxicity of silver. Crit Rev Toxicol 2007;37:237–50.CrossrefGoogle Scholar

  • 119.

    Hussain SM, Javorina AK, Schrand AM, Duhart HM, Ali SF, Schlager JJ. The interaction of manganese nanoparticles with PC-12 cells induces dopamine depletion. Toxicol Sci 2006;92:456–63.Google Scholar

  • 120.

    Mirsattari SM, Hammond RR, Sharpe MD, Leung FY, Young GB. Myoclonic status epilepticus following repeated oral ingestion of colloidal silver. Neurology 2004;62:1408–10.CrossrefGoogle Scholar

  • 121.

    Miresmaeili SM, Halvaei I, Fesahat F, Fallah A, Nikonahad N, Taherinejad M. Evaluating the role of silver nanoparticles on acrosomal reaction and spermatogenic cells in rat. Iran J Reprod Med 2013;11:423–30.Google Scholar

  • 122.

    Braydich-Stolle LK, Lucas B, Schrand A, Murdock RC, Lee T, Schlager JJ, et al. Silver nanoparticles disrupt GDNF/Fyn kinase signaling in spermatogonial stem cells. Toxicol Sci 2010;116:577–89.CrossrefGoogle Scholar

  • 123.

    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.CrossrefGoogle Scholar

  • 124.

    Garcia TX, Costa GM, Franca LR, Hofmann MC. Sub-acute intravenous administration of silver nanoparticles in male mice alters Leydig cell function and testosterone levels. Reprod Toxicol 2014;45C:59–70.CrossrefGoogle Scholar

  • 125.

    Austin CA, Umbreit TH, Brown KM, Barber DS, Dair BJ, Francke-Carroll S, et al. Distribution of silver nanoparticles in pregnant mice and developing embryos. Nanotoxicology 2012;6:912–22.CrossrefGoogle Scholar

  • 126.

    Hong JS, Kim S, Lee SH, Jo E, Lee B, Yoon J, et al. Combined repeated-dose toxicity study of silver nanoparticles with the reproduction/developmental toxicity screening test. Nanotoxicology 2014;8:349–62.CrossrefGoogle Scholar

  • 127.

    De Jong WH, Van Der Ven LT, Sleijffers A, Park MV, Jansen EH, Van Loveren H, et al. Systemic and immunotoxicity of silver nanoparticles in an intravenous 28 days repeated dose toxicity study in rats. Biomaterials 2013;34:8333–43.CrossrefGoogle Scholar

  • 128.

    Buzea C, Pacheco, II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Biointerphases 2007;2:MR17–71.Google Scholar

  • 129.

    Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005;113:823–39.CrossrefGoogle Scholar

  • 130.

    Shin SH, Ye MK, Kim HS, Kang HS. The effects of nano-silver on the proliferation and cytokine expression by peripheral blood mononuclear cells. Int Immunopharmacol 2007;7:1813–8.CrossrefGoogle Scholar

  • 131.

    Heydarnejad MS, Rahnama S, Mobini-Dehkordi M, Yarmohammadi P, Aslnai H. Sliver nanoparticles accelerate skin wound healing in mice (Mus musculus) through suppression of innate immune system. Nanomedicine J 2014;1:79–87.Google Scholar

  • 132.

    Chi Z, Liu R, Zhao L, Qin P, Pan X, Sun F, et al. A new strategy to probe the genotoxicity of silver nanoparticles combined with cetylpyridine bromide. Spectrochim Acta A Mol Biomol Spectrosc 2009;72:577–81.CrossrefGoogle Scholar

  • 133.

    Yang W, Shen C, Ji Q, An H, Wang J, Liu Q, et al. Food storage material silver nanoparticles interfere with DNA replication fidelity and bind with DNA. Nanotechnology 2009;20:085102.CrossrefGoogle Scholar

  • 134.

    Demir E, Vales G, Kaya B, Creus A, Marcos R. Genotoxic analysis of silver nanoparticles in Drosophila. Nanotoxicology 2011;5:417–24.CrossrefGoogle Scholar

  • 135.

    Schmaehl D, Steinhoff D. Studies on cancer induction with colloidal silver and gold solutions in rats. Z Krebsforsch 1960;63:586–91.Google Scholar

  • 136.

    Bouwmeester H, Dekkers S, Noordam MY, Hagens WI, Bulder AS, de Heer C, et al. Review of health safety aspects of nanotechnologies in food production. Regul Toxicol Pharmacol 2009;53:52–62.CrossrefGoogle Scholar

  • 137.

    Furst A, Schlauder MC. Inactivity of two noble metals as carcinogens. J Environ Pathol Toxicol 1978;1:51–7.Google Scholar

  • 138.

    Foldbjerg R, Dang DA, Autrup H. Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549. Arch Toxicol 2011;85:743–50.Google Scholar

  • 139.

    Jiang X, Foldbjerg R, Miclaus T, Wang L, Singh R, Hayashi Y, et al. Multi-platform genotoxicity analysis of silver nanoparticles in the model cell line CHO-K1. Toxicol Lett 2013;222:55–63.Google Scholar

  • 140.

    Guo D, Zhao Y, Zhang Y, Zhou H, Ge Y, Ma W, et al. The cellular uptake and cytotoxic effect of silver nanoparticles on chronic myeloid leukemia cells. J Biomed Nanotechnol 2014;10:669–78.CrossrefGoogle Scholar

  • 141.

    Guo D, Zhu L, Huang Z, Zhou H, Ge Y, Ma W, et al. Anti-leukemia activity of PVP-coated silver nanoparticles via generation of reactive oxygen species and release of silver ions. Biomaterials 2013;34:7884–94.CrossrefGoogle Scholar

  • 142.

    Seil JT, Webster TJ. Antimicrobial applications of nanotechnology: methods and literature. Int J Nanomedicine 2012;7:2767–81.Google Scholar

  • 143.

    Christensen FM, Johnston HJ, Stone V, Aitken RJ, Hankin S, Peters S, et al. Nano-silver – feasibility and challenges for human health risk assessment based on open literature. Nanotoxicology 2010;4:284–95.CrossrefGoogle Scholar

  • 144.

    Korani M, Rezayat SM, Ghamami SG. Silver nanoparticle induced muscle abnormalities: a sub-chronic dermal assessment in guinea pig. J Pharmaceut Health Sci 2012;1:21–9.Google Scholar

About the article

Mitra Korani

Mitra Korani obtained her Master’s degree in Toxicology from Tehran University of Medical Sciences. She is currently a PhD student in Pharmaceutical Nanotechnology at Mashhad University of Medical Sciences, Mashhad, Iran.

Elham Ghazizadeh

Elham Ghazizadeh obtained her Master’s degree in Molecular Genetic from National Institute of Genetic Engineering and Biotechnology. She is currently a PhD student in Medicine Biotechnology at Mashhad University of Medical Sciences, Mashhad, Iran.

Shahla Korani

Shahla Korani obtained her Bachelor degree in Biology from Razi University of Kermanshah (1995). She received post graduate degree in Biochemistry from the Islamic Azad University of Tehran, Research and Study branch (2005). Since 2013, she has been a PhD student in Molecular Medicine at Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Zahra Hami

Zahra Hami obtained her Bachelor’s degree in Pure Chemistry from the University of Isfahan, Iran. She finished her Master’s degree in Toxicology followed by PhD in Medical Nanotechnology from Tehran University of Medical Sciences, Iran. Her research interest lies in combining her knowledge in toxicology and nanotechnology (i.e., Nanotoxicology) for medical applications.

Afshin Mohammadi-Bardbori

Afshin Mohammadi-Bardbori obtained his PhD in toxicology from the Karolinska Institutet of Sweden in 2013. Now he is an Assistant Professor at the Shiraz University of Medical Sciences, School of Pharmacy. His current research interest in the field of nonotoxicology focuses on the biological effects of manufactured nanomaterials on human health.


Corresponding author: Afshin Mohammadi-Bardbori, PhD, Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, 7146864685 Shiraz, Iran, E-mail: ,


Received: 2014-09-25

Accepted: 2014-12-02

Published Online: 2015-01-17

Published in Print: 2015-01-01


Conflict of interest statement

Declaration of interest: The authors declare no conflicts of interest.


Citation Information: European Journal of Nanomedicine, ISSN (Online) 1662-596X, ISSN (Print) 1662-5986, DOI: https://doi.org/10.1515/ejnm-2014-0032.

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