Toxicity Of Nanosilver Research Articles

Effect of light on toxicity of nanosilver to Tetrahymena pyriformis

More and more silver nanoparticles (AgNPs) have been released into the aquatic environment due to their widespread use, which may result in harmful effects on aquatic organisms. Environmental risk assessments of AgNPs on aquatic organisms in the natural environment (including light, sound, etc.) are indispensable. The aim of the present study was to elucidate the influence of light on the toxicity of AgNPs to Tetrahymena pyriformis. Silver nanoparticles, which were synthesized by reduction of silver nitrate with sodium borohydride, ranged in size from 5 to 20 nm with most particles approximately 10 nm. The authors performed AgNPs toxicity assays under a simulated natural environment with sunlight. The results indicated that the toxicity of AgNPs is higher than silver ion in the environment without light, but under the light condition, the toxicity of AgNPs decreased greatly. After 24 h of incubation with AgNPs, the inhibition ratio was 69.2 ± 7% in the dark and 35.5 ± 2% in the light, and the degree of inhibition was reduced by 33.7%. However, the effect of light on Ag(+) could be negligible. Further investigation indicated that the light irradiation could induce the growth of AgNPs and sequentially form bulk agglomeration. This decreased the surface area and the number of bare Ag atoms, resulting in a slower release rate and less Ag(+) ions released from AgNPs. At the same time, bulk agglomeration induced the deposition of part of the AgNPs to the aquatic bottom, which decreased the amount of AgNPs existing in water. All these phenomena led to the weakened toxicity of AgNPs in a light irradiation environment.

Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans

Toxicity of nano-formulated silver to eukaryotes was assessed by exposing nematodes (Caenorhabditis elegans) to two types of silver nanoparticles (AgNPs): with average primary particle diameters of 1nm (AgNP1) and 28nm (AgNP28, PVP coated), respectively. Tests were performed with and without presence of Escherichia coli to evaluate how the presence of a food bacterium affects the AgNP toxicity. A pre-exposure experiment was also conducted with nematodes pre-exposed to 0 and 1mgAgNPL−1, respectively, for 20h prior to exposure at higher concentrations of AgNP. Both AgNP1 and AgNP28 showed adverse dose-response effects and mortality on C. elegans. LC50 for AgNP28 was lower than for AgNP1 and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic than AgNP1. Including E. coli in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when bacteria were not present. Pre-exposure to a low-level AgNP1 concentration made the nematodes slightly more sensitive to further exposure at higher concentrations compared to no pre-exposure, indicating that nematodes have no efficient physiological ability to counteract nano-silver toxicity by acclimation. The amount of dissolved Ag+ was 0.18 to 0.21mgL−1 after 20h at the highest AgNP1 (10mgL−1) and AgNP28 (3mgL−1) doses in the exposure medium, respectively. The upper limit of Ag+ solubility cannot immediately explain the dose-response-related toxic effects of the AgNP nor the difference between AgNP1 and AgNP28. Higher toxicity of AgNP28 than AgNP1 may be explained by a combination of effects of coating, Ag-solubility and higher uptake rates due to agglomeration into μm-size agglomerates in the exposure medium.

Effects of natural water chemistry on nanosilver behavior and toxicity to Ceriodaphnia dubia and Pseudokirchneriella subcapitata

The success of nanotechnology will undoubtedly lead to the increased introduction of nanoparticles (NPs) into natural systems, and aquatic systems will likely act as sinks for these new pollutants. Differences in the chemistry of these aquatic systems will control changes in surface properties of NPs and therefore could impact their environmental fate and toxicity. A series of batch experiments was conducted to determine the effect of natural waters with different solution chemistries on nanosilver (nAg) particle dispersion, stability, and toxicity. Toxicity assays were performed in tested natural waters as well as in traditional growth media. Briefly, nAg suspended in a natural water with a low ionic strength/dissolved organic carbon (DOC) ratio had an average particle size of 76.8 ± 0.4 nm and was less toxic to Ceriodaphnia dubia and Pseudokirchneriella subcapitata (median lethal concentration [LC50] = 221 ppb and median inhibition concentration [IC50] = 1,600 ppb, respectively), whereas a natural water with a high ionic strength/DOC ratio had an average particle size of 192 ± 5.1 nm and produced a much higher toxicity response (LC50 = 0.433 ppb and IC50 = 22.6 ppb, respectively). These findings help to establish needed correlations between water-matrix-dependent nAg particle properties and toxicity implications and indicate that the use of traditional growth media in toxicity assays concerning engineered NPs might not always be appropriate.

In vitro effect of Nanosilver toxicity on fibroblast and mesenchymal stem cell lines

Nanotechnology presents countless opportunities to develop new and improved consumer products for the benefit of the society. A most prominent nanoproduct is nanosilver. Nanosilver particles are generally smaller than 100 nm and contain 20–15,000 silver atoms. Despite the wide application of nanomaterials, there is a serious lack of information concerning their impact on human health. In the previous study we reported the cytotoxic of nanosilver on osteoblast G292 cancer cell line and the amount of IC50 determined as 3.42 µg/ml (Moaddab et al., Iran. Nano Lett., Vol. 1, No. 1, January 2011, pp. 11-16). The purpose of the present study is to assess the biological assay of nanosilver on two normal cell lines of fibroblast (HF2), and mesenchymal stem cells. The effect of nanosilver on these cells is evaluated by light microscopy, and by cell proliferation and standard cytotoxicity assays. The results demonstrate a concentration-dependent toxicity for the cells tested, and IC50 was determined as 6.33, and 6.68 µg/ml in mesenchymal stem cell, and fibroblast HF2, respectively. There is no significant difference between the 24 h and 48 h of cells exposure to nanosilver. The results show that Nano-Ag possesses low toxicity to normal cells and can display potential application in cancer chemoprevention and chemotherapy.

Differential toxicity of silver and titanium dioxide nanoparticles on Drosophila melanogaster development, reproductive effort, and viability: Size, coatings and antioxidants matter

Silver and titanium dioxide nanoparticles are known to induce oxidative stress in vitro and in vivo. Here we test if they impact development, mating success, and survivorship in Drosophila melanogaster, and if so, if these effects are reversible by antioxidants. Ingestion of nanotitanium dioxide during the larval stage of the life cycle showed no effects on development or survivorship, up to doses of 200μgmL−1. Conversely, ingestion of nanosilver had major dose, size, and coating-dependent effects on each of these aspects of life history. Each of these effects was partially or fully reversible by vitamin C. Larvae growing on nanosilver supplemented with vitamin C showed a greater than twofold increase in survivorship compared to flies reared on nanosilver alone, and a threefold increase in mating success. Vitamin C also rescued cuticular and pigmentation defects in nanosilver fed flies. Biochemical assays of superoxide dismutase and glutathione show these markers respond to nanotitanium dioxide and nanosilver induced oxidative stress, and this response is reduced by vitamin C. These results indicate that life history effects of nanosilver ingestion result from oxidative stress, and suggest antioxidants as a potential remediation for nanosilver toxicity. Conversely, the lack of nanotitanium dioxide life history toxicity shows that oxidative stress does not necessarily result in whole organism effects, and argues that nanoparticle toxicity needs to be examined at different levels of biological organization.

Acute and subchronic dermal toxicity of nanosilver in guinea pig

Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver) have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 μg/mL) in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 μg/mL) in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater tissue abnormalities than the subjects of acute tests. It seems that colloidal nanosilver has the potential to provide target organ toxicities in a dose- and time-dependent manner.

Controlled Release of Biologically Active Silver from Nanosilver Surfaces

Major pathways in the antibacterial activity and eukaryotic toxicity of nanosilver involve the silver cation and its soluble complexes, which are well established thiol toxicants. Through these pathways, nanosilver behaves in analogy to a drug delivery system, in which the particle contains a concentrated inventory of an active species, the ion, which is transported to and released near biological target sites. Although the importance of silver ion in the biological response to nanosilver is widely recognized, the drug delivery paradigm has not been well developed for this system, and there is significant potential to improve nanosilver technologies through controlled release formulations. This article applies elements of the drug delivery paradigm to nanosilver dissolution and presents a systematic study of chemical concepts for controlled release. After presenting thermodynamic calculations of silver species partitioning in biological media, the rates of oxidative silver dissolution are measured for nanoparticles and macroscopic foils and used to derive unified area-based release kinetics. A variety of competing chemical approaches are demonstrated for controlling the ion release rate over 4 orders of magnitude. Release can be systematically slowed by thiol and citrate ligand binding, formation of sulfidic coatings, or the scavenging of peroxy-intermediates. Release can be accelerated by preoxidation or particle size reduction, while polymer coatings with complexation sites alter the release profile by storing and releasing inventories of surface-bound silver. Finally, the ability to tune biological activity is demonstrated through a bacterial inhibition zone assay carried out on selected formulations of controlled release nanosilver.

Nanosilver as a new generation of nanoproduct in biomedical applications

Nanosilver (NS), comprising silver nanoparticles, is attracting interest for a range of biomedical applications owing to its potent antibacterial activity. It has recently been demonstrated that NS has useful anti-inflammatory effects and improves wound healing, which could be exploited in developing better dressings for wounds and burns. The key to its broad-acting and potent antibacterial activity is the multifaceted mechanism by which NS acts on microbes. This is utilized in antibacterial coatings on medical devices to reduce nosocomial infection rates. Many new synthesis methods have emerged and are being evaluated for NS production for medical applications. NS toxicity is also critically discussed to reflect on potential concerns before widespread application in the medical field.

Interactions of nanosilver with Escherichia coli cells in planktonic and biofilm cultures

Biofilms are often more resistant to toxic chemicals such as heavy metals and antimicrobial agents than planktonic cells. Nanosilver has a broad range of applications with strong antimicrobial activity. However, biofilm susceptibility to nanosilver toxicity is not well understood. We studied the bacterial activity in planktonic or biofilm cultures after nanosilver exposure using oxygen quenching fluorescence-based microrespirometry. We also determined the aggregation behavior and the spatial distribution of nanosilver having red fluorescence in biofilms of Escherichia coli expressing green fluorescent protein. At the same bacterial concentrations (3 × 10 8 CFU/mL), biofilms were about four times more resistant to nanosilver inhibition than planktonic cells. The minimum bactericidal concentrations (MBCs) of nanosilver (size from 15 to 21 nm), defined as the lowest concentration that kills at least 99.9% of a planktonic or biofilm bacterial population, were 38 and 10 mg/L Ag, respectively. For comparison, silver ions were more toxic to E. coli than nanosilver with MBCs of 2.4 and 1.2 mg/L Ag for planktonic and biofilm cultures, respectively. Nanosilver was aggregated in the presence of planktonic or biofilm-forming cells resulting in an increase of average particle size by a factor of 15 and 40, respectively. The nanosilver particles were able to penetrate to approximately 40 μm in a thick biofilm after 1-h exposure. These findings suggested that biofilm resistance to nanosilver could be at least partially due to nanoparticle aggregation and retarded silver ion/particle diffusion.

Role of sulfide and ligand strength in controlling nanosilver toxicity

Nanosilver has been used broadly in nanotechnology enhanced consumer products because of its strong antimicrobial properties. Silver nanoparticles (AgNPs) released from these products will likely enter wastewater collection and treatment systems. This research evaluated the role of sulfide and ligand strength in controlling nanosilver toxicity to nitrifying bacteria that are important in wastewater treatment. The nanosilver toxicity in the absence and presence of ligands (SO 4 2−, S 2−, Cl −, PO 4 3−, and EDTA −) commonly present in wastewater was determined from the oxygen uptake rate measurements. Sulfide appeared to be the only ligand to effectively reduce nanosilver toxicity. By adding a small aliquot of sulfide that was stoichiometrically complexed with AgNPs, the nanosilver toxicity to nitrifying organisms was reduced by up to 80%. Scanning electron microscopy coupled with energy dispersive X-ray analysis indicated that AgNPs were highly reactive with sulfide to form new Ag xS y complexes or precipitates. These complexes were not oxidized after a prolonged period of aeration (18 h). This information is useful for wastewater treatment design and operation to reduce nanosilver toxicity via sulfide complexation. While the biotic ligand model was successful in predicting the toxicity of Ag + ions, it could not accurately predict the toxicity of AgNPs. Nevertheless, it could be one of the many tools useful in predicting and controlling nanosilver toxicity to wastewater microorganisms.

Food storage material silver nanoparticles interfere with DNA replication fidelity and bindwith DNA

Nanosilver is increasingly used in the food industry and biomedical applications. A lot ofstudies have been done to investigate the potential toxicity of nanosilver. But informationon whether or how nanosilver particles bring changes in genetic materials remains scant. Inthis study, the replication fidelity of the rpsL gene was quantified when nanosilver particleswere present in polymerase chain reactions (PCRs) or cell cultures of E. coli transformedwith the wild-type rpsL gene. Three types of nanosilver (silver nanopowder, SN;silver–copper nanopowder, SCN; and colloidal silver, CS) were tested. The results showedthat the replication fidelity of the rpsL gene was differentially compromised by all threekinds of nanosilver particle compared with that without nanosilver. This assay could beexpanded and applied to any other materials to preliminarily assess their potentiallong-term toxicity as a food additive or biomedical reagent. Moreover, we found thatnanosilver materials bind with genomic DNA under atomic force microscopy,and this might be an explanation for the compromised DNA replication fidelity.

Size Dependent and Reactive Oxygen Species Related Nanosilver Toxicity to Nitrifying Bacteria

The intrinsic slow growth of nitrifying bacteria and their high sensitivity to environmental perturbations often result in cell growth inhibition by toxicants. Nanoparticles are of great concern to the environment because of their small size and high catalytic properties. This work sought to determine size-dependent inhibition by Ag nanoparticles and evaluate the relationship between the inhibition and reactive oxygen species (ROS). Nanoparticles with an average size range of 9-21 nm were synthesized by varying the molar ratios of BH4-/Ag+ in the solution. The resulting ROS generation was quantified in the presence and absence of the bacteria while the degree of inhibition was inferred from specific oxygen uptake rate measurements, determined by extant respirometry. By examining the correlation between nanoparticle size distribution, photocatalytic ROS generation, intracellular ROS accumulation, and nitrification inhibition, we observed that inhibition to nitrifying organisms correlated with the fraction of Ag nanoparticles less than 5 nm in the suspension. It appeared that these size nanoparticles could be more toxic to bacteria than any other fractions of nanoparticles or their counterpart bulk species. Furthermore, inhibition by Ag nanoparticles as well as other forms of silver (AgCl colloid and Ag+ ion) correlated well with the intracellular ROS concentrations, but not with the photocatalytic ROS fractions. The ROS correlations were different for the different forms of silver, indicating that factors other than ROS are also important in determining nanosilver toxicity.

The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells

Nanomaterials and nanoparticles have received considerable attention recently because of their unique properties and diverse biotechnology and life sciences applications. Nanosilver products, which have well-known antimicrobial properties, have been used extensively in a range of medical settings. Despite the widespread use of nanosilver products, relatively few studies have been undertaken to determine the biological effects of nanosilver exposure. The purpose of this study was to evaluate the toxicity of nanosilver and to elucidate possible molecular mechanisms underlying the biological effects of nanosilver. Here, we show that nanosilver is cytotoxic, inducing apoptosis in NIH3T3 fibroblast cells. Treatment with nanosilver induced the release of cytochrome c into the cytosol and translocation of Bax to mitochondria, indicating that nanosilver-mediated apoptosis is mitochondria-dependent. Nanosilver-induced apoptosis was associated with the generation of reactive oxygen species (ROS) and JNK activation, and inhibition of either ROS or JNK attenuated nanosilver-induced apoptosis. In nanosilver-resistant HCT116 cells, up-regulation of the anti-apoptotic proteins, Bcl-2 appeared to be associated with a diminished apoptotic response. Taken together, our results provide the first evidence for a molecular mechanism of nanosilver cytotoxicity, showing that nanosilver acts through ROS and JNK to induce apoptosis via the mitochondrial pathway.