Toxicity Of Silver Nanoparticles Research Articles

Effective combinations of silver nanoparticles and antimicrobial peptides against antibiotic-resistant bacteria

BACKGROUND: The problem of constantly growing resistance of microorganisms to the antibiotics used forces scientists to constantly search for new antimicrobial agents. AIM: To study the antimicrobial activity and toxicity of silver nanoparticles and antimicrobial peptides with a β-hairpin structure, and to characterize their combined antimicrobial action. MATERIALS AND METHODS: The antimicrobial activity of silver nanoparticles and antimicrobial peptides against antibiotic-resistant bacteria was assessed by serial dilutions in a liquid nutrient medium, and the combined antimicrobial activity – by serial dilutions according to the “checkerboard” method. The toxicity of the substances to human cells was determined using a hemolytic test. RESULTS: The studied silver nanoparticles have pronounced antimicrobial activity and low toxicity to human erythrocytes. Silver nanoparticles containing acetylcysteine are more active against gram-negative bacteria than against gram-positive ones. Synergism of the antibacterial action was detected with the combined use of silver nanoparticles stabilized with sodium oleate and protegrin-1. A synergistic antimicrobial effect was also noted for combinations of silver nanoparticles containing acetylcysteine with protegrin-1, ricaecilin and shuchin-4. CONCLUSIONS: Effective combinations of silver nanoparticles and antimicrobial peptides have been identified that act synergistically against antibiotic-resistant bacterial strains, i.e. they multiply the effect of each other. These combinations can be used as prototypes for the development of antibacterial drugs.

Presence of microplastics enhanced the toxicity of silver nanoparticles on the collembolan Folsomia candida

There is growing interest in interactions of microplastics (MPs) with other pollutants. However, there is limited understanding of the combined effects of MPs and silver nanoparticles (AgNPs) on nontarget soil organisms. This work aimed to examine the effects of exposure to various AgNPs' concentrations alone (0, 0.1, 1, 10, 100, 1000 mg·kg-1, 50 nm) and in combination with polyvinyl chloride microplastics (PVC MPs, 80-250 μm) at 0.1% concentration for 28 days on reproduction, Ag accumulation, C/N ratio, and isotopic fractionation of the standard soil fauna collembolan Folsomia candida. Results showed that compared to the AgNPs exposure alone, the presence of MPs significantly reduced reproduction by 51.4% and markedly increased Ag content in collembolans by 87.7% at 1000 mg·kg-1 AgNPs, which evidenced a synergistic effect. Co-exposure to MPs and AgNPs resulted in a noticeable reduction in the C/N ratio in F. candida body tissues by 9.90% and 5.27% at 1 and 10 mg·kg-1 AgNPs, respectively, showing additive and synergistic effects. Additionally, this co-exposure altered stable isotope fractionation, with the highest increments of δ15N by 32.3% and inhibition of δ13C by 2.62%, demonstrating the turnover of nutrients shift in the collembolan tissues. Collectively, this study demonstrates that con-current exposure to environmentally relevant concentration of MPs and relatively high doses of AgNPs synergistically induces toxic effects on F. candida, leading to Ag accumulation and reproduction decline. These findings imply that MPs could alter collembolans' responses to AgNPs exposure, potentially enhancing the metal ions' bioavailability in soil environments and posing ecotoxicological threats to soil-dwelling organisms.

Antibacterial Efficacy of Tryptophan Coordinated Silver Nanoparticles Against E. coli: Spectroscopic and Microscopic Evaluation of Bacterial Cell Death.

The capability of conventional fluorescence spectroscopy and right-angled synchronous fluorescence spectroscopy (SFS) was evaluated to quantify the antibacterial potential of chemically synthesized Tryptophan coordinated silver nanoparticles (Ag-TrpNPs). Silver nanoparticles have gained significant importance as a material of interest due to their diverse assemblies in the nanoscale range and their potent antibacterial activity. But due to toxicity of silver nanoparticles there is a dire need to coordinate these materials with some biocompatible and biodegradable molecules. The study has been focused on chemical synthesis of functional fluorescence nanomaterials based on Tryptophan molecules coordinated with silver nanoparticles (Ag-TrpNPs). The antibacterial activity of Ag-TrpNPs was assessed in bacteria due to their functional characteristics such as tuneability, biocompatibility, and bioavailability. We employed optical characterization techniques such as Ultraviolet-visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), fluorescence spectroscopy, and confocal microscopy to ensure the particles formation in aqueous suspension. DLS analysis confirmed the hydrodynamic size of the nanoparticles of approximately 100nm. SEM images revealed the spherical morphology and size distribution of the Ag-TrpNPs. Escherichia coli bacterial strains were used to assess the antibacterial efficacy of the Ag-TrpNPs using fluorescence spectroscopy and imaging. Initially, the agar well plate method was employed to evaluate the antimicrobial activity of the Ag-TrpNPs. The significant zones of inhibition of size 37mm at 500µg/mL and 27mm at 15.5µg/mL were reported which indicated the efficiency of Ag-TrpNPs from higher to lower concentration. Conventional and synchronous fluorescence spectra provided evidence of bacterial cell death in aqueous suspensions to ensure the interaction of Ag-TrpNPs with E. coli bacteria at different times and concentrations. SEM was employed to investigate the interaction mechanism between Ag-TrpNPs and bacterial cells. The images revealed cell wall disintegration, leading to the leakage of cellular contents, and eventually cell death occurred.

Enhancement of Triple-Negative Breast Cancer-Specific Induction of Cell Death by Silver Nanoparticles by Combined Treatment with Proteotoxic Stress Response Inhibitors.

Metal nanoparticles have been tested for therapeutic and imaging applications in pre-clinical models of cancer, but fears of toxicity have limited their translation. An emerging concept in nanomedicine is to exploit the inherent drug-like properties of unmodified nanomaterials for cancer therapy. To be useful clinically, there must be a window between the toxicity of the nanomaterial to cancer and toxicity to normal cells. This necessitates identification of specific vulnerabilities in cancers that can be targeted using nanomaterials without inducing off-target toxicity. Previous studies point to proteotoxic stress as a driver of silver nanoparticle (AgNPs) toxicity. Two key cell stress responses involved in mitigating proteotoxicity are the heat shock response (HSR) and the integrated stress response (ISR). Here, we examine the role that these stress responses play in AgNP-induced cytotoxicity in triple-negative breast cancer (TNBC) and immortalized mammary epithelial cells. Furthermore, we investigate HSR and ISR inhibitors as potential drug partners to increase the anti-cancer efficacy of AgNPs without increasing off-target toxicity. We showed that AgNPs did not strongly induce the HSR at a transcriptional level, but instead decreased expression of heat shock proteins (HSPs) at the protein level, possibly due to degradation in AgNP-treated TNBC cells. We further showed that the HSR inhibitor, KRIBB11, synergized with AgNPs in TNBC cells, but also increased off-target toxicity in immortalized mammary epithelial cells. In contrast, we found that salubrinal, a drug that can sustain pro-death ISR signaling, enhanced AgNP-induced cell death in TNBC cells without increasing toxicity in immortalized mammary epithelial cells. Subsequent co-culture studies demonstrated that AgNPs in combination with salubrinal selectively eliminated TNBCs without affecting immortalized mammary epithelial cells grown in the same well. Our findings provide additional support for proteotoxic stress as a mechanism by which AgNPs selectively kill TNBCs and will help guide future efforts to identify drug partners that would be beneficial for use with AgNPs for cancer therapy.

Investigation of the biological activity and toxicity of bioactive silver nanoparticles synthesized via Vitex agnus-castus seed extract on honey bees.

In this study, silver nanoparticles (AgNPs) coated with bioactive molecules were synthesized via Vitex agnus-castus L. (VAC) seed extract (VAC/AgNPs). The synthesized VAC/AgNPs were characterized by surface plasmon resonance (SPR) ultraviolet-visible region spectroscopy (UV-Vis). The hydrodynamic size and surface charge analysis of the particles were measured with a Zeta sizer. The results of UV-Vis and Zeta analysis revealed that AgNPs were synthesized, the size distribution was nanoscale, and the solution was stable. The effects of the synthesized VAC/AgNPs and aqueous extract of VAC seeds on honeybees were investigated by means of lifespan test and histopathological analysis. It was determined that both VAC seed extract and VAC/AgNPs were non-toxic to honeybees at certain doses, positively affected their life span and contributed to their longevity in the life span test. Furthermore, no adverse effects were detected in terms of intestinal health in histopathological examinations. Therefore, VAC/AgNPs are considered to be a promising bioactive agent for honeybees.

Stereological and biochemical effects of thymoquinone on ovarian tissue toxicity induced by silver nanoparticles in NMRI mice: An experimental study.

The toxicity of silver nanoparticles (AgNPs) has been proven in the female reproductive system. Thymoquinone (TQ) is a natural antioxidant and bioactive component of Nigella sativa. We evaluated the efficacy of TQ on ovarian tissue following toxicity induced by AgNPs in female mice. 24 female NMRI mice (5-6 wk, an average weight of 33 gr) were randomly divided into 4 groups (n = 6/each): control, AgNPs (500 mg/kg, gavage), TQ (2.5 mg/kg, intraperitoneal injection), and TQ+AgNPs. Mice were treated every day for 35 days. Serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), luteinizing hormone, and follicle-stimulating hormone were measured. The optical disector and stereological techniques were utilized to estimate the follicular count, their volume at different developmental stages, and the structure of ovarian tissue. In the AgNPs group, the serum concentrations of TAC (p = 0.01), luteinizing hormone (p 0.001), follicle-stimulating hormone, the volume of corpus luteum (p 0.001), and the number of follicles decreased significantly compared to the control group. Nevertheless, AgNPs significantly increased the MDA level. In the TQ+AgNPs group compared to the AgNPs group, a significant decrease in MDA level (p 0.001) and a significant improvement in TAC (p = 0.03), and hormonal levels, the number of primary, preantral, and antral follicles (p = 0.04), and the volume of corpus luteum (p = 0.01) were observed. TQ improved the number of follicles by reducing oxidative stress and lipid peroxidation in AgNPs-damaged ovarian tissue.

Dynamics of Phytotoxicity Indicators of Ordinary Chernozem when it is Contaminated with Silver Nanoparticles

The dynamics of phytotoxicity indicators (germination and length of radish roots) of ordinary chernozem when contaminated with silver nanoparticles was studied. In laboratory conditions, ordinary chernozem was contaminated with silver nanoparticles (1, 10 and 100 mg/kg) for 3, 10, 30, 90 and 180 days. It was found that the more silver nanoparticles were introduced into the soil, the greater the decrease in germination and length of radish roots. There was no restoration of germination and length of radish roots with an increase in the period from the moment of contamination. In this study, the maximum toxic period from the moment of contamination for each indicator was identified by its sensitivity to silver nanoparticles and informativeness. The maximum toxicity of silver nanoparticles in relation to the root length and germination of radishes was noted on the 10th and 30th days, respectively. The results can be used to assess the phytotoxicity of soils contaminated with silver nanoparticles.

Effects of changed water regime on the toxicity of silver nanoparticles (AgNPs) in tadpoles of Fejervarya limnocharis.

Climate change is viewed as one of the important causes of the amphibian population decline. Aspects of climate change like increase in water temperature and drying up of habitats have been underrepresented. The expanding production and usage of metal nanoparticles like silver nanoparticles (AgNPs) make them likely to end up in aquatic ecosystems. To arrive at a realistic assessment of the impact of AgNPs in a warming world, we have investigated the effects of temperature on the acute toxicity of AgNPs in tadpoles of Fejervarya limnocharis at 24, 48, 72 and 96h of exposure. The various aspects of sub-lethal toxicities of AgNPs with increase in temperature were also investigated. Besides, the effects of habitat desiccation on the sub-lethal toxicities of AgNPs in the tadpoles were analysed. The LC50 values of AgNPs at four different time points were found to be significantly different between the two different temperatures. Alterations in survival pattern, life history traits, amplifications in genotoxic potential and oxidative stress were observed with increased water temperature following AgNP exposure. The phenomenon of habitat desiccation was also found to significantly affect the toxicity of AgNPs with respect to alterations in mortality rate, time to metamorphosis and morphometric parameters of metamorphosed tadpoles. The findings suggest that changed water regime such as increased water temperature as well as reduction in water level accelerated the toxic effects of AgNPs in F. limnocharis tadpoles which is likely to affect their natural populations.

Tiny silver bullets: silver nanoparticles are insecticidal to Culicoides sonorensis (Diptera: Ceratopogonidae) biting midge larvae.

Insecticide formulations with safer environmental profiles and limited off-target effects are desirable to manage medical and veterinary pests. Silver nanoparticles are insecticidal against mosquitos, nonbiting midges, and other insects. The biting midge, Culicoides sonorensis Wirth and Jones, is a vector of agriculturally important pathogens in much of the United States, and this study aimed to examine the insecticidal properties of silver nanoparticles in larvae of this species. Mortality of third-instar larvae was assessed daily for 7 days after exposure to concentrations of silver nanoparticles, sorghum polymer particles, and hybrid silver-sorghum polymer particles. Both silver nanoparticles and silver-sorghum polymer particles were insecticidal, but sorghum polymer particles alone did not significantly contribute to larval mortality. Concentrations of 100mg/liter of silver nanoparticles achieved >50% mortality at day 7, and 200mg/liter treatments achieved >75% larval mortality within 24h. The antimicrobial properties of silver nanoparticles were also examined, and culturable bacteria were recovered from larval-rearing media at 200mg/liter but not at 400mg/liter of silver nanoparticles. These data suggest that C. sonorensis larval mortality is primarily caused by silver nanoparticle toxicity and not by the reduction of bacteria (i.e., a larval food source). This work describes the first use of silver nanoparticles in C. sonorensis and shows the potential insecticide applications of these nanoparticles against this agricultural pest. The grain-polymer particles also successfully carried insecticidal silver nanoparticles, and their utility in loading diverse compounds could be a novel toxin delivery system for biting midges and similar pests.

Soil type dependent toxicity of AgNM300K can be predicted by internal concentrations in earthworms

A continuous challenge in nanotoxicology is the interaction of nanoparticles with the soil components. In the present study, we compare the toxicity of silver nanoparticles (AgNM300K) on earthworms across 4 different soils, exploring which among the total-, soil solution-, or worm tissue-Ag-concentrations that enables the best prediction of toxicity across the soils. We exposed the earthworm Eisenia fetida to AgNM300K for 56 days to assess survival, reproduction, and bioaccumulation. These endpoints were related to measurements of Ag-ions and -nanoparticles in soil, soil solution, and in the worm tissue. Tested soils included the standard OECD, LUFA 2.2, Hygum, and RefSol 01A soils. Toxicity was strongly dependent on the soil type, highly correlated with the organic matter, clay, and Cation Exchange Capacity (CEC). CEC provided the best correlation with the internal silver concentrations across the soils. The soil solution did not provide useful predictions across the soils.

Acute Toxicity, Anti-diabetic, and Anti-cancerous Potential of Trillium Govanianum-conjugated Silver Nanoparticles in Balb/c Mice.

The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale because Cancer and Diabetes mellitus are major concerns in developing countries. Therefore, in vitro and in vivo antidiabetic and anti-cancerous activities of Trillium govanianum conjugated silver nanoparticles were assessed. In the current study synthesis of silver nanoparticles using Trillium govanianum and characterization were done using a scanning electron microscope, UV-visible spectrophotometer, and FTIR analysis. The in vitro and in vivo anti-diabetic and anti-cancerous potential (200 mg/kg and 400 mg/kg) were carried out. It was discovered that Balb/c mice did not show any major alterations during observation of acute oral toxicity when administered orally both TGaqu (1000 mg/kg) and TGAgNPs (1000 mg/kg), and results revealed that 1000 mg/kg is not lethal dose as did not find any abnormalities in epidermal and dermal layers when exposed to TGAgNPs. In vitro studies showed that TGAgNPs could not only inhibit alpha-glucosidase and protein kinases but were also potent against the brine shrimp. Though, a significant reduction in blood glucose levels and significant anti-cancerous effects was recorded when alloxan-treated and CCl4-induced mice were treated with TGAgNPs and TGaqu. Both in vivo and in vitro studies revealed that TGaqu and TGAgNPs are not toxic at 200 mg/kg, 400 mg/kg, and 1000 mg/kg doses and possess strong anti-diabetic and anti-cancerous effects due to the presence of phyto-constituents. Further, suggesting that green synthesized silver nanoparticles could be used in pharmaceutical industries to develop potent therapeutic agents.

Surface Charge-Modulated Toxicity of Cysteine-Stabilized Silver Nanoparticles.

The toxicity of silver nanoparticles (AgNPs) depends on their physicochemical properties. The ongoing research aims to develop effective methods for modifying AgNPs using molecules that enable control over the processes induced by nanoparticles in both normal and cancerous cells. Application of amino acid-stabilized nanoparticles appears promising, exhibiting tunable electrokinetic properties. Therefore, this study focused on determining the influence of the surface charge of cysteine (CYS)-stabilized AgNPs on their toxicity towards human normal B (COLO-720L) and T (HUT-78) lymphocyte cell lines. CYS-AgNPs were synthesized via the chemical reduction. Transmission electron microcopy (TEM) imaging revealed that they exhibited a quasi-spherical shape with an average size of 18 ± 3 nm. CYS-AgNPs remained stable under mild acidic (pH 4.0) and alkaline (7.4 and 9.0) conditions, with an isoelectric point observed at pH 5.1. Following a 24 h treatment of lymphocytes with CYS-AgNPs, concentration-dependent alterations in cell morphology were observed. Positively charged CYS-AgNPs notably decreased lymphocyte viability. Furthermore, they exhibited grater genotoxicity and more pronounced disruption of biological membranes compared to negatively charged CYZ-AgNPs. Despite both types of AgNPs interacting similarly with fetal bovine serum (FBS) and showing comparable profiles of silver ion release, the biological assays consistently revealed that the positively charged CYS-AgNPs exerted stronger effects at all investigated cellular levels. Although both types of CYS-AgNPs have the same chemical structure in their stabilizing layers, the pH-induced alterations in their surface charge significantly affect their biological activity.

Bridging the Gap Between Human Toxicology and Ecotoxicology Under One Health Perspective by a Cross-Species Adverse Outcome Pathway Network for Reproductive Toxicity.

Although ecotoxicological and toxicological risk assessments are performed separately from each other, recent efforts have been made in both disciplines to reduce animal testing and develop predictive approaches instead, for example, via conserved molecular markers, and in vitro and in silico approaches. Among them, adverse outcome pathways (AOPs) have been proposed to facilitate the prediction of molecular toxic effects at larger biological scales. Thus, more toxicological data are used to inform on ecotoxicological risks and vice versa. An AOP has been previously developed to predict reproductive toxicity of silver nanoparticles via oxidative stress on the nematode Caenorhabditis elegans (AOPwiki ID 207). Following this previous study, our present study aims to extend the biologically plausible taxonomic domain of applicability (tDOA) of AOP 207. Various types of data, including in vitro human cells, in vivo, and molecular to individual, from previous studies have been collected and structured into a cross-species AOP network that can inform both human toxicology and ecotoxicology risk assessments. The first step was the collection and analysis of literature data to fit the AOP criteria and build a first AOP network. Then, key event relationships were assessed using a Bayesian network modeling approach, which gave more confidence in our overall AOP network. Finally, the biologically plausible tDOA was extended using in silico approaches (Genes-to-Pathways Species Conservation Analysis and Sequence Alignment to Predict Across Species Susceptibility), which led to the extrapolation of our AOP network across over 100 taxonomic groups. Our approach shows that various types of data can be integrated into an AOP framework, and thus facilitates access to knowledge and prediction of toxic mechanisms without the need for further animal testing. Environ Toxicol Chem 2024;00:1-14. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

In vitro antimicrobial activity of silver nanoparticles against selected Gram-negative and Gram-positive pathogens.

Infections caused by pathogenic bacteria increase patient morbidity and mortality and significantly raise treatment costs. The use of silver nanoparticles as an alternative treatment for S aureus, E coli, MRSA, E faecalis, K pneumoniae and P aeruginosa indicates their antibacterial effect and prompts medical research to consider the next generation of antibacterial drugs that could change antibiotic therapy. By combining silver nanoparticles with different classes of antibiotics, the antibacterial effect is evidenced by increased values of the inhibition zone compared to the values obtained for some antibiotics commonly used in the treatment of bacterial infections. This study focuses on comparing the antibacterial activity of antibiotics versus antibiotics combined with silver nanoparticles against various bacteria, by comparing inhibition zones obtained for both. We aim to prove that the size of the inhibition zone for antibiotics combined with silver nanoparticles is greater, thus confirming the improved antibacterial effect. In this study we tested the antibacterial activity of solutions of silver nanoparticles alone or in combination with different antibiotics. We used standard bacterial strains, ATCC, both Gram positive bacteria Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, as well as Gram negative bacteria Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, but also on clinical isolates: a strain MRSA (Methicillin Resistant Staphylococcus aureus) and a PDR strain (pan drug resistant) of Klebsiella pneumoniae. Bacterial identification was performed using Vitek MS analyzer (bioMerieux). Antibiotic susceptibility determination was performed with VITEK2 COMPACT SYSTEM (bio Merieux, Inc Durham NC) with ready to use VITEK AST cards. The interpretation of the results was done in compliance with EUCAST 2023-2024 standards. Testing was performed for several classes of antibiotics, silver nanoparticle solutions in 2 concentrations (10 μg/mL and 100 μg/mL) and for combinations of antibiotics with silver nanoparticle solutions. The diameter of the inhibition zone (ZOI) for silver nanoparticles, antibiotics and silver nanoparticles combined with antibiotic against each bacterium was expressed in millimeters. The Kirby-Bauer disk-diffusion method, in accordance with current EUCAST standards, was used to analyze the antibacterial effect of antibiotics, silver nanoparticles, and antibiotics combined with silver nanoparticles at biocompatible doses of 10 and 100 μg/mL. The experiments were conducted in triplicate, and the results were almost identical. The results of this study show that the silver nanoparticles displayed antibacterial activity, proven by the appearance of the inhibition zone, in various sizes, for all bacteria studied. The antibiotic classes tested were beta-lactamins, first, second, third and fourth generation cephalosporins, macrolides, fluoroquinolones, lincosamides, aminoglycosides, glycopeptides, tetracyclines, oxazolidinones, sulfonamides, rifamycins, amphenicols. Testing S aureus ATCC 29213, the highest zone of inhibition was demonstrated for cephalosporins (32.6667 ± 0.701 mm), macrolides (31.6667 ± 0.701 mm, and lincosamides (29.6667 ± 0.701 mm). Testing MRSA (internal code GR0333), the highest zone of inhibition for combination of silver nanoparticles and antibiotics was demonstrated for fluoroquinolones (36.3333 ± 0.701 mm), lincosamides (32.3333 ± 0.701 mm), Fusid acid (32.3333 ± 0.701 mm) and aminoglicosides (31.3333 ± 0.701 mm). Testing E coli ATCC 25922 the highest zone of inhibition was for Fosfomycine, 39 mm and for E faecalis ATCC 29212 for aminoglicosides was 19 mm. For K pneumoniae (internal code GQ8575) the inhibition zone for silver nanoparticles 100 μg/mL was 12.3333 ± 0.701 mm and for P aeruginosa ATCC 27253 was 16 ± 1.214 mm. The use of metallic nanoparticles, especially silver ones, as antimicrobial agents with definite bactericidal activity has led medical specialists to consider this new treatment which may change antibacterial therapy. Studies of in vitro combinations between silver nanoparticles and different classes of antibiotics represent a highly efficient and effective new antibacterial treatment against multidrug-resistant bacteria. To avoid the problem of antimicrobial resistance associated with conventional antibiotics, it is necessary to understand the adaptive mechanisms of bacteria under the action of metal nanoparticles, which could be exploited in future studies. Further in vitro and in vivo studies that would assess specify the biocompatibility and toxicity of silver nanoparticles will make these super nanomaterials the medicines of the future.

Hepatotoxicity of silver nanoparticles: Benchmark concentration modeling of an in vitro transcriptomics study in human iPSC-derived hepatocytes

Despite two decades of research on silver nanoparticle (AgNP) toxicity, a safe threshold for exposure has not yet been established, albeit being critically needed for risk assessment and regulatory decision-making. Traditionally, a point-of-departure (PoD) value is derived from dose response of apical endpoints in animal studies using either the no-observed-adverse-effect level (NOAEL) approach, or benchmark dose (BMD) modeling. To develop new approach methodologies (NAMs) to inform human risk assessment of AgNPs, we conducted a concentration response modeling of the transcriptomic changes in hepatocytes derived from human induced pluripotent stem cells (iPSCs) after being exposed to a wide range concentration (0.01–25 μg/ml) of AgNPs for 24 h. A plausible transcriptomic PoD of 0.21 μg/ml was derived for a pathway related to the mode-of-action (MOA) of AgNPs, and a more conservative PoD of 0.10 μg/ml for a gene ontology (GO) term not apparently associated with the MOA of AgNPs. A reference dose (RfD) could be calculated from either of the PoDs as a safe threshold for AgNP exposure. The current study illustrates the usefulness of in vitro transcriptomic concentration response study using human cells as a NAM for toxicity study of chemicals that lack adequate toxicity data to inform human risk assessment.

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF SILVER NANOPARTICLES: SYSTEMATIC REVIEW

Silver is exploited for the benefit of mankind from past centuries. Silver has been proved to be much more powerful when compared to other metallic nanoparticles, not only bactericidal properties but it is also effective against eukaryotic microorganisms and viruses. Creation of Ag Nanoparticles has increased the silver efficacy many folds due to their physical and chemical properties, especially the surface area to volume ratio is most important imparting the antibacterial activity over various microorganisms. To lessen bacterial infections in incurable wounds nanocrystalline silver dressings, creams, gels are formulated. However, several problems are associated with the use. Silver nanoparticle toxicity is a major threat associated with their use and the inhibition of beneficiary microorganisms due to lack of specificity of silver nanoparticles is environmentalist’s concern. To reduce the threats associated, there should be a careful assessment of the silver nanoparticles release into the environment and should be regulated. It has to be noted that novel methods to produce silver nanoparticles which reduce the toxicity and other associated threats has to be developed in the future to exploit the vast capabilities of the silver nanoparticles for the benefit of mankind. As technology advancement is always in demand with changing environmental conditions, the present review will focus on the synthesis and antibacterial properties of silver nanoparticles along with its environmental impact. Key Words: Silver nanoparticles ∙ Antibacterial Activity ∙ Microorganisms ∙ Environmental Impact

The Role of Phthalocyanine-Gold Nanoconjugates (Pc-Au NCs) in Ameliorating the Hepatic and Renal Toxicity-Induced by Silver Nanoparticles (Ag NPs) in Male Rats.

Recently, gold nanoparticles (Au Nps) have gained tremendous attention for its unique properties as a safe nanocarrier for delivering drugs that are used in different disease diagnoses. Although silver nanoparticles (Ag NPs) have been generally applied due to their strong antibacterial, antiviral, antifungal, and antimicrobial properties, their toxicity is a subject of sustained debate, thus requiring further studies. The present study aims to evaluate the potential protective effect of gold nanoparticles and phthalocyanine-gold nanoconjugates (Pc-Au NCs) against the hepatorenal toxicity of silver nanoparticles in male rats. Herein, 60 adult male Rattus norvegicus rats were divided into six equal groups (n = 10/group); the first group was kept as control, the second received gold nanoparticles (Au NPs) intraperitoneally (10 µg/kg) daily for 3 weeks, the third group is gold-phthalocyanine (Pc-Au) group where rats were injected intraperitoneally with gold-phthalocyanine for 3 weeks (10 µg/kg), the fourth group received silver nanoparticles (Ag NPs) (4 mg/kg) daily intraperitoneally for 3 weeks, the fifth group is silver + gold nanoparticles group (Ag + Au), and the sixth is silver + gold-phthalocyanine nanoconjugates (Ag + Pc-Au) group in which rats were intraperitoneally injected firstly with Ag NPs (4 mg/kg) for 3 weeks then with gold or gold-phthalocyanine for another 3 weeks (10 µg/kg). Our results revealed that Ag NPs could increase the serum AST, ALT, ALP, urea, creatinine, and lipid profile and significantly decreased the total protein and albumin. Moreover, histopathological alterations detected in the kidney and the liver of the Ag NPs group included vascular congestion, inflammatory cell infiltration, and tissue distortion. Alongside, exposure to Ag NPs induces hepatic and renal oxidative stress by suppressing the antioxidant-related genes including glutathione peroxidase 1 (gpx1), superoxide dismutase (sod), and catalase (cat). Ag NPs also upregulated the hepatic and renal genes involved in inflammation such as the interleukin-6 (il-6) and tumor necrosis factor-α (tnf-α), nuclear factor kappa B (nf-κβ), apoptosis such as the BCL2 associated X (bax), casp3, and other related to metabolism including asparagine synthetase (asns), suppressor of cytokine signaling 3 (socs3), MYC proto-oncogene (myc), and C-C motif chemokine ligand 2 (ccl2). On the other hand, treatment with Au NPs and Pc-Au NCs could effectively ameliorate the hepatorenal damages induced by Ag NPs and improve liver and kidney architecture and function, especially in the Pc-Au NCs group. Briefly, our study revealed the underlined mechanism of Ag NPs hepatotoxic and nephrotoxic effects and that Pc-Au NCs could alleviate these adverse impacts via their anti-oxidative, anti-apoptotic, and anti-inflammatory activities.

Silver nanoparticles forensic uses and toxicity on vital organs and different body systems

This study aimed to investigate the forensic uses and potential toxicity of silver nanoparticles on vital organs and different body systems. A systematic review methodology was used to identify and critically evaluate the literature on the forensic uses of silver nanoparticles in different fields and to assess their potential toxicity on various vital organs and body systems. The study found that silver nanoparticles have potential forensic uses, particularly in forensic biology and forensic toxicology, but there are concerns about their potential toxicity. The study recommends further research on the mechanisms of toxicity of silver nanoparticles and the development of safe and effective strategies for their use in forensic science. The study’s strengths include its systematic review methodology and use of multiple databases, while limitations include a limited time frame and focus on English language publications. Future research should focus on investigating the potential risks of silver nanoparticle exposure for forensic professionals.

Synthesis, Characterization, Acute Dermal Toxicity, Anti-inflammatory, and Wound Healing Potential of Biogenic Silver Nanoparticles in Balb C Mice.

The current study aimed to develop an economic plant-based therapeutic agent to improve the treatment strategies for diseases at the nano-scale. In the current research, silver nanoparticles were synthesized using Trillium govanianum aqueous extract. Characterizations were done using UV-visible spectrophotometer, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. In vivo biological activities such as acute dermal toxicity, wound healing, and anti-inflammatory were done on Balb C mice. Absorbance at 295 nm corresponds to the out-of-plane quadrupole Plasmonresonance while at 350 nm corresponds to in-plane dipole resonance. SEM images showed the morphology of TGAgNPs is not exactly spherical while XRD analysis shows that highly crystalline TGAgNPs with an average size of 27.94 nm. The FTIR spectrum represents sharp peaks of aldehyde, amide I, aromatic rings, and polysaccharides. The microscopic assessment did not find any epidermal and dermal layer abnormalities in Blab C mice when exposed to TGAgNPs during acute dermal toxicity. Results revealed that 1000 mg/kg is not a lethal dose. In the wound healing activity, no mortality and no abnormal signs were observed when petroleum jelly, nitrofuranose, TGaqu, and TGAgNPs-based ointments were applied. Enhanced epithelization was recorded in TGaqu and TGAgNPs treated mice (p≤0.001). The wound contraction percentage was higher in nitrofuranose-treated mice (74%) followed by TGAgNPs (71%), and TGaqu (69%) compared to vehicle-treated and open-wounded mice. The paw edema model proved the potential use of TGAgNPs and TGaqu as anti-inflammatory agents. Hence, the results proved that both TGaqu and TGAgNPs are not toxic and possessed strong anti-inflammatory and wound-healing effects due to the presence of phytochemical constituents and could be used in various drug production as a therapeutic agent.

Green Synthesis, Lead Toxicity and Pharmacokinetic Evaluation of Sumac Silver Nanoparticles In Vivo

Green Synthesis, Lead Toxicity and Pharmacokinetic Evaluation of Sumac Silver Nanoparticles In Vivo