Evaluation of the Effects of Particle Sizes of Silver Nanoparticles on Various Biological Systems

Seven biological methods were adopted (three bacterial activities of bioluminescence, enzyme, enzyme biosynthetic, algal growth, seed germination, and root and shoot growth) to compare the toxic effects of two different sizes of silver nanoparticles (AgNPs). AgNPs showed a different sensitivity in each bioassay. Overall, the order of inhibitory effects was roughly observed as follows; bacterial bioluminescence activity ≈ root growth > biosynthetic activity of enzymes ≈ algal growth > seed germination ≈ enzymatic activity > shoot growth. For all bacterial activities (bioluminescence, enzyme, and enzyme biosynthesis), the small AgNPs showed statistically significantly higher toxicity than the large ones (p < 0.0036), while no significant differences were observed among other biological activities. The overall effects on the biological activities (except shoot growth) of the small AgNPs were shown to have about 4.3 times lower EC₅₀ (high toxicity) value than the large AgNPs. These results also indicated that the bacterial bioluminescence activity appeared to be an appropriate method among the tested ones in terms of both sensitivity and the discernment of particle sizes of AgNPs.     

Dispersion stability of citrate- and PVP-AgNPs in biological media for cytotoxicity test

Silver nanoparticles (AgNPs) with antimicrobial property have been used for years in various applications, such as antibacterial coating and air/water purification to eliminate microorganisms. In recent years, a number of studies on the potential risk of nanomaterials in humans and the environment have appeared, and thus a large number of studies regarding the toxic effects of AgNPs on cells and micro-organisms have been reported. In in-vivo and in-vitro cytotoxicity tests, various biological media are used, and thus the dispersion stability of AgNPs in media is important to a successful toxicity test. Therefore, we investigated the dispersion stability of AgNPs in various biological media; PBS (phosphate buffered saline), FBS (fetal bovine serum), and de-ionized water (pH 2, 7, and 9) with and without photo-irradiation. Herein, citrate and PVP (polyvinylpyrrolidone) stabilized AgNPs were used as target materials. In short- and long-term stability tests, we found that PVP-AgNPs stabilized by steric hindrance have good dispersion stability in biological media, compared to citrate-AgNPs stabilized by electrostatic repulsion.     

斑马鱼模型评价BCG-CpG-DNA的安全性

目的用斑马鱼模型对BCG-CpG-DNA进行安全性评价。方法以斑马鱼胚胎为实验材料,将BCG-CpG-DNA设置4个浓度组(0.15、1.5、15、75 mg/L),暴露斑马鱼,以胚胎培养液暴露为空白对照组,以三甲基氯化锡(TMT)和全氟辛烷磺酸盐(PFOS)暴露为阳性对照组,胚胎期6 hp(f受精后6 h)脱膜,8 hpf进行暴露毒性实验,研究其对斑马鱼发育、遗传、免疫以及行为的毒性影响。每组做3个重复,试验重复3次。结果未观察到BCG-CpG-DNA各浓度组的斑马鱼胚胎明显的畸形和孵化死亡情况,其自主运动、触摸运动、行为检测、免疫强度检测与空白对照组相比,差异均无统计学意义(P>0.05)。TMT对照组暴露对斑马鱼生长、发育、免疫及其神经等均有不同程度的影响,导致心胞肿大,对光暗刺激反应敏感,相对荧光强度明显增强,嗜中性粒细胞数量增多,对炎症的敏感性增强,与空白对照组相比,差异有统计学意义(P<0.05)。结论 BCG-CpG-DNA暴露对斑马鱼生长、发育、免疫及其神经均无明显的急性毒性作用,在斑马鱼的胚胎暴露中具有较好的安全性。     

Co-Treatment of Copper Oxide Nanoparticle and Carbofuran Enhances Cardiotoxicity in Zebrafish Embryos

The use of chemicals to boost food production increases as human consumption also increases. The insectidal, nematicidal and acaricidal chemical carbofuran (CAF), is among the highly toxic carbamate pesticide used today. Alongside, copper oxide nanoparticles (CuO) are also used as pesticides due to their broad-spectrum antimicrobial activity. The overuse of these pesticides may lead to leaching into the aquatic environments and could potentially cause adverse effects to aquatic animals. The aim of this study is to assess the effects of carbofuran and copper oxide nanoparticles into the cardiovascular system of zebrafish and unveil the mechanism behind them. We found that a combination of copper oxide nanoparticle and carbofuran increases cardiac edema in zebrafish larvae and disturbs cardiac rhythm of zebrafish. Furthermore, molecular docking data show that carbofuran inhibits acetylcholinesterase (AChE) activity in silico, thus leading to impair cardiac rhythms. Overall, our data suggest that copper oxide nanoparticle and carbofuran combinations work synergistically to enhance toxicity on the cardiovascular performance of zebrafish larvae.     

Advances in Nanotechnology towards Development of Silver Nanoparticle-Based Wound-Healing Agents

Since antiquity, silver-based therapies have been used in wound healing, wound care and management of infections to provide adequate healing. These therapies are associated with certain limitations, such as toxicity, skin discolouration and bacterial resistance, which have limited their use. As a result, new and innovative wound therapies, or strategies to improve the existing therapies, are sought after. Silver nanoparticles (AgNPs) have shown the potential to circumvent the limitations associated with conventional silver-based therapies as described above. AgNPs are effective against a broad spectrum of microorganisms and are less toxic, effective at lower concentrations and produce no skin discolouration. Furthermore, AgNPs can be decorated or coupled with other healing-promoting materials to provide optimum healing. This review details the history and impact of silver-based therapies leading up to AgNPs and AgNP-based nanoformulations in wound healing. It also highlights the properties of AgNPs that aid in wound healing and that make them superior to conventional silver-based wound treatment therapies.     

Effect of agglomeration of silver nanoparticle on nanotoxicity depression

Silver nanoparticles (AgNPs) are used commercially in a variety of applications, including textiles, cosmetics, spray cleaning agents, and metal products. AgNP itself, however, is classified as an environmental hazard by Environmental Protection Agency (EPA, USA) Nanotechnology White Paper, due to its toxic, persistent and bioaccumulative characteristics when exposed to the environment. We investigated the cumulative mortality and abnormalities in Japanese medaka (Oryziaslatipes) embryos after exposure to AgNPs. Free AgNPs in solution have a high activity with respect to biological interactions regarding blocking blood flow and distribution of AgNPs into the cells from head to tail of hatched O. latipes. Interestingly, the agglomeration of AgNPs (loss of nanosized characteristics) played an important role in the environmental toxicity. The present study demonstrated that when the AgNPs were exposed in the ecosystem and then formed agglomerates, nanotoxicity was reduced.     

Nanoparticles Targeting Innate Immune Cells in Tumor Microenvironment

A variety of innate immune cells such as macrophages, dendritic cells, myeloid-derived suppressor cells, natural killer cells, and neutrophils in the tumor microenvironments, contribute to tumor progression. However, while several recent reports have studied the use of immune checkpoint-based cancer immunotherapy, little work has focused on modulating the innate immune cells. This review focuses on the recent studies and challenges of using nanoparticles to target innate immune cells. In particular, we also examine the immunosuppressive properties of certain innate immune cells that limit clinical benefits. Understanding the cross-talk between tumors and innate immune cells could contribute to the development of strategies for manipulating the nanoparticles targeting tumor microenvironments.     

Human Intestinal Tissue Explant Exposure to Silver Nanoparticles Reveals Sex Dependent Alterations in Inflammatory Responses and Epithelial Cell Permeability

Consumer products manufactured with antimicrobial silver nanoparticles (AgNPs) may affect the gastrointestinal (GI) system. The human GI-tract is complex and there are physiological and anatomical differences between human and animal models that limit comparisons between species. Thus, assessment of AgNP toxicity on the human GI-tract may require tools that allow for the examination of subtle changes in inflammatory markers and indicators of epithelial perturbation. Fresh tissues were excised from the GI-tract of human male and female subjects to evaluate the effects of AgNPs on the GI-system. The purpose of this study was to perform an assessment on the ability of the ex vivo model to evaluate changes in levels of pro-/anti-inflammatory cytokines/chemokines and mRNA expression of intestinal permeability related genes induced by AgNPs in ileal tissues. The ex vivo model preserved the structural and biological functions of the in-situ organ. Analysis of cytokine expression data indicated that intestinal tissue of male and female subjects responded differently to AgNP treatment, with male samples showing significantly elevated Granulocyte-macrophage colony-stimulating factor (GM-CSF) after treatment with 10 nm and 20 nm AgNPs for 2 h and significantly elevated RANTES after treatment with 20 nm AgNPs for 24 h. In contrast, tissues of female showed no significant effects of AgNP treatment at 2 h and significantly decreased RANTES (20 nm), TNF-α (10 nm), and IFN-γ (10 nm) at 24 h. Smaller size AgNPs (10 nm) perturbed more permeability-related genes in samples of male subjects, than in samples from female subjects. In contrast, exposure to 20 nm AgNPs resulted in upregulation of a greater number of genes in female-derived samples (36 genes) than in male-derived samples (8 genes). The ex vivo tissue model can distinguish sex dependent effects of AgNP and could serve as a translational non-animal model to assess the impacts of xenobiotics on human intestinal mucosa.     

Bacterial uptake of silver nanoparticles in the presence of humic acid and AgNO3

Silver nanoparticles (AgNPs), potent antibiotic materials, have been found to cause cell-membrane damage and produce reactive oxygen species (ROS). The resultant structural change in the cell-membrane could cause an increase in cell permeability of silver ions and AgNPs. To address this issue further, in-vivo and in-vitro cytotoxicity testing of as-made nanomaterials was conducted to quantify and assess their nanotoxicity. Considering the behavior of AgNPs in the environment, toxicity may be reflected by differences in their physicochemical properties (size, agglomeration rate, adsorption properties on humic acid) dependency and toxicity depression. Therefore, we investigated the effect of the cellular uptake of AgNPs with the kinetics of agglomeration and adsorption. The amount of agglomerated and adsorbed AgNPs with sizes of <14 nm was higher than that for AgNPs with sizes of 90 and 140 nm. For 90 and 140 nm sized AgNPs, adsorption was more significant than agglomeration. It is noteworthy that the normal concept that smaller sized AgNPs are taken up more readily may be in error in cases of interactions of abiotic factors.     

Effects of Nanotoxicity on Female Reproductivity and Fetal Development in Animal Models

The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein.     

Synthesis of novel poly(1-naphthylamine)-silver nanocomposites and its catalytic studies on reduction of 4-nitrophenol and methylene blue

A novel poly(1-naphthylamine)-silver (PNA-Ag) nanocomposite has been prepared and used as a heterogeneous catalyst for the reduction of 4-nitrophenol (4-NP) and methylene blue (MB). In this study, silver nanoparticles (AgNPs) have been incorporated to PNA via a simple and fast one-step route, where PNA acts as the reductant for silver ions and stabilizer for AgNPs. The prepared PNA-Ag nanocomposites were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), thermogravimetric analysis (TGA), energy dispersive X-ray scattering (EDAX), and Fourier transform infrared (FTIR) spectroscopy. They provided ample evidence for the anchoring of AgNPs to the PNA chains. Enhanced electrochemical performance of the PNA-Ag nanocomposite has been evidenced by cyclic voltammetry studies. Catalytic studies confirmed that the rate of reduction of both 4-NP and MB with sodium borohydride have been enhanced significantly in the presence of AgNPs loaded PNA in comparison to neat PNA. This nanocomposite could find application as catalyst for reductive degradation of toxic organic pollutants. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48318.     

Rapid biological synthesis of silver nanoparticles using Kalopanax pictus plant extract and their antimicrobial activity

Silver nanoparticles (AgNPs) have promising potential in biomedicine, energy science, optics, and health care applications. We synthesized AgNPs using plant, Kalopanax pictus leaf extract. UV-visible spectrophotometric study showed the characteristic peak for AgNPs at wavelength 430 nm. The optical density at 430 nm increased after addition of plant leaf extract, indicating increase in formation of nanoparticles. Comparative time course analyses for AgNP synthesis carried out at different reaction temperatures (20, 60, and 90 °C) revealed higher reaction rate for K. pictus than Magnolia kobus plant leaf extract, which showed highest AgNP synthesis rate in the previous report. Electron microscopy analyses confirmed the presence of well dispersed AgNPs, predominantly with spherical shapes. In transmission electron microscopy, the particle size decreased with increase in temperature. Electron dispersive X-ray spectroscopy analyses indicated that Ag content increased with increase in reaction temperature. Fourier transform-infrared spectroscopy studies revealed capping of bioorganics from plant to the synthesized AgNPs. The antimicrobial activity of the synthesized AgNPs against Escherichia coli increased with increase in reaction temperature. The observations in this study will prove beneficial in approaching rapid synthesis of AgNPs and their antimicrobial application.     

Phyto-synthesized silver nanoparticles for biological applications

Silver nanoparticles (AgNPs) are valuable metal nanoparticles that exhibit exceptional properties compared to their bulk materials. Pronounced surface area, quantum confinement effect complemented by small particle dimension, and many other extraordinary characteristics make AgNPs suitable in a variety of applications. Different methods have been adopted to synthesize AgNPs. Biological methods can formulate AgNPs in an environmentally friendly manner without producing toxic waste. Among the biological methods, plants are simple and attractive sources for AgNP synthesis. Compared to AgNPs produced via other modes of synthesis, phyto-synthesized AgNPs, due to their safety features, have been found to be advantageous for a variety of applications, especially biological applications. Strong research efforts have investigated the utility of phyto-synthesized AgNPs for different applications. Investigators are coming up with innovative applications of phyto-synthesized AgNPs for the development of science and technology and to benefit humankind. The present article focuses on phyto-synthesized AgNPs for biological applications, with a brief review of their synthesis, mechanism, and size/shape control.     

Surface plasmon resonance study of (positive, neutral, negative) vesicles rupture by AgNPs’ attack for screening of cytotoxicity induced by nanoparticles

As the use of nanomaterials in industrial and commercial applications is growing, official reports concerning possible environmental and health effects of nanoparticles are also steadily increasing. Many toxicological studies on the adverse effects of silver nanoparticles (AgNPs) have used living organisms, which is a time consuming process. Therefore, we propose an alternative method to assess the in-vivo and in-vitro cytotoxicity of nanomaterials, involving a fast and simple screening procedure for vesicle rupture or fusion by the attack of AgNPs. With the assumption that particle interaction between AgNPs and vesicles is induced by electrostatic repulsion or attraction of surface charge, three vesicles with different charges (positive, neutral, and negative) were prepared and they were dispersed with AgNPs in different pH (3, 7, and 10) solutions to control the surface charge of AgNPs. Based on the results of vesicle rupture analyzed by SPR and TEM, screening of cell rupture through vesicles by AgNPs’ attack is determined to be most suitable at pH 7.     

Enhanced antibacterial and anti-biofilm activities of silver nanoparticles against Gram-negative and Gram-positive bacteria

Silver nanoparticles (AgNPs) have been used as antibacterial, antifungal, antiviral, anti-inflammtory, and antiangiogenic due to its unique properties such as physical, chemical, and biological properties. The present study was aimed to investigate antibacterial and anti-biofilm activities of silver nanoparticles alone and in combination with conventional antibiotics against various human pathogenic bacteria. Here, we show that a simple, reliable, cost effective and green method for the synthesis of AgNPs by treating silver ions with leaf extract of Allophylus cobbe. The A. cobbe-mediated synthesis of AgNPs (AgNPs) was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Furthermore, the antibacterial and anti-biofilm activity of antibiotics or AgNPs, or combinations of AgNPs with an antibiotic was evaluated using a series of assays: such as in vitro killing assay, disc diffusion assay, biofilm inhibition, and reactive oxygen species generation in Pseudomonas aeruginosa, Shigella flexneri, Staphylococcus aureus, and Streptococcus pneumonia. The results suggest that, in combination with antibiotics, there were significant antimicrobial and anti-biofilm effects at lowest concentration of AgNPs using a novel plant extract of A. cobbe, otherwise sublethal concentrations of the antibiotics. The significant enhancing effects were observed for ampicillin and vancomycin against Gram-negative and Gram-positive bacteria, respectively. These data suggest that combining antibiotics and biogenic AgNPs can be used therapeutically for the treatment of infectious diseases caused by bacteria. This study presented evidence of antibacterial and anti-biofilm effects of A. cobbe-mediated synthesis of AgNPs and their enhanced capacity against various human pathogenic bacteria. These results suggest that AgNPs could be used as an adjuvant for the treatment of infectious diseases.     

Early and Delayed Impact of Nanosilver on the Glutamatergic NMDA Receptor Complex in Immature Rat Brain

Silver nanoparticles (AgNPs) are the one of the most extensively used nanomaterials. The strong antimicrobial properties of AgNPs have led to their use in a wide range of medical and consumer products. Although the neurotoxicity of AgNPs has been confirmed, the molecular mechanisms have not been extensively studied, particularly in immature organisms. Based on information gained from previous in vitro studies, in the present work, we examine whether ionotropic NMDA glutamate receptors contribute to AgNP-induced neurotoxicity in an animal model of exposure. In brains of immature rats subjected to a low dose of AgNPs, we identified ultrastructural and molecular alterations in the postsynaptic region of synapses where NMDA receptors are localized as a multiprotein complex. We revealed decreased expression of several NMDA receptor complex-related proteins, such as GluN1 and GluN2B subunits, scaffolding proteins PSD95 and SynGAP, as well as neuronal nitric oxide synthase (nNOS). Elucidating the changes in NMDA receptor-mediated molecular mechanisms induced by AgNPs, we also identified downregulation of the GluN2B-PSD95-nNOS-cGMP signaling pathway which maintains LTP/LTD processes underlying learning and memory formation during development. This observation is accompanied by decreased density of NMDA receptors, as assessed by a radioligand binding assay. The observed effects are reversible over the post-exposure time. This investigation reveals that NMDA receptors in immature rats are a target of AgNPs, thereby indicating the potential health hazard for children and infants resulting from the extensive use of products containing AgNPs.     

Comparison of mechanical properties of heat‐polymerized acrylic resin with silver nanoparticles added at different concentrations and sizes

The aim of this study was to investigate the effect of silver nanoparticles (AgNPs) incorporation on the flexural strength (FS) of poly(methyl methacrylate) (PMMA). PMMA specimens (65 mm × 10 mm × 3.3 mm for flexural test, 50 mm × 6 mm × 4 mm for impact test) containing different sizes (40, 50, 60 nm) and concentrations (0.05%, 0.2%) of AgNPs were prepared, along with a control group with no AgNP. Impact strength (IS) and FS of all specimens were measured, and one‐way ANOVA and Tukey–Kramer post hoc multiple comparisons tests were used to identify any statistical differences between groups. The addition of AgNPs has no effect on IS of PMMA. The incorporation of AgNPs affected the FS of PMMA depending on the concentration of nanoparticles. The addition of large‐sized nanoparticles to PMMA increases its FS. Accordingly, adding AgNP with proper concentrations to PMMA may enhance the mechanical properties of denture bases used in clinical practice. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45807.     

Green synthesis of silver nanoparticles using plant extracts

The strategy for design of new nanometals was developed due to their wide applications in many fields. One of the most important nanometals is silver nanoparticles (AgNPs) because of their extensive applications in biotechnology and biomedical fields. AgNPs were usually synthesized by using chemical and physical methods. In the chemical methods, various toxic chemicals are used, which are harmful to the health of living organisms. Therefore, the AgNPs were synthesized by using biological methods based on green chemistry for reducing the toxic chemicals. There are various resources for green synthesis of AgNPs, such as bacteria, fungi, enzyme and plant extracts. The green synthesis of AgNPs involves three main steps: the selection of the solvent medium, the selection of environmentally reducing agents, and the selection of non-toxic substances for the stability of AgNPs. The biosynthesis of AgNPs using plant extracts is more favorable than other biological methods because of removing the elaborate process of maintaining cell cultures. It can be also suitably scaled up for large scale production of AgNPs. This review focuses on green synthesis of AgNPs using various plant extracts.     

Mangrove-mediated synthesis of silver nanoparticles using native Avicennia marina plant extract from southern Iran

The development of eco-friendly and nontoxic processes for the synthesis of nanoparticles is one of the most important discussed issues in nanotechnology science. This study reports the green synthesis of silver nanoparticles (AgNPs) using aqueous extract of leaf, stem, and root of Avicennia marina, the native and dominant mangrove plant in southern Iran. Among the different plant parts, the extract of leaves yielded the maximum synthesis of AgNPs. Synthesized AgNPs were investigated using UV–visible spectrophotometry, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), energy-dispersive spectroscopy (EDS), and Fourier transform infrared (FTIR) spectroscopy. Absorption spectrum in 420?nm confirmed the synthesis of AgNPs. TEM images revealed that the synthesized AgNPs had the same spherical morphology with a size range between 0 and 75?nm. The distribution size histogram indicated that the most frequent particles were in the range of 10–15?nm and the mean size of nanoparticles was 17.30?nm. The results of SEM image showed nanoparticles with a size range between 15 and 43?nm. XRD pattern indicated the crystalline nature of synthesized nanoparticles. EDS results confirmed the presence of elements like silver, carbon, chlorine, nitrogen, and oxygen in the nanoparticles produced from leaf extract. Silver had the maximum percentage of formation, 51.6%. FTIR indicated the presence of different functional groups such as amines, alcohol, alkanes, phenol, alkyl halides, and aromatic loops in the synthesis process. Green biosynthesis of AgNPs using aqueous extract of native A. marina appears rapid, reliable, nontoxic, and eco-friendly.     

Physicochemical properties between pristine and aged AgNPs for the evaluation of nanotoxicity

The use of nanomaterials in industrial and commercial applications is growing, and official reports concerning the possible environmental and health effects of nanoparticles are steadily increasing. An understanding of the potential toxicity of nanomaterials is important for creating sustainable and safe nanotechnologies. To test the cytotoxicity of nanomaterials, quantitative and qualitative analyses of raw nanomaterials should be priorities. However, the fundamental properties of raw materials will change compared to those of aged materials in biological media due to the interaction between nanomaterials and media composition. Therefore, the correlation and interdependence between pristine physicochemical properties (PChem) of raw nanomaterials before the toxicity test and aged PChem in biological media were evaluated using modified test guidelines originally suggested by the OECD WPMN (Organization for Economic Cooperation and Development, Working Party on Manufactured Nanomaterials) for peer-reviewed papers concerning silver nanoparticles, during the period of 2005 to 2010. In addition, we investigated whether the suggested analysis tools are applicable to define the PChem of AgNPs with regard to cytotoxicity.