In vitro evaluation of the toxicity and underlying molecular mechanisms of Janus Fe3O4‐TiO2 nanoparticles in human liver cells

Recent studies show that Janus Fe₃O₄‐TiO₂ nanoparticles (NPs) have potential applications as a multifunctional agent of magnetic resonance imaging (MRI) and photodynamic therapy (PDT) for the diagnosis and therapy of cancer. However, little work has been done on their biological effects. To evaluate the toxicity and underlying molecular mechanisms of Janus Fe₃O₄‐TiO₂ nanoparticles, an in vitro study using a human liver cell line HL‐7702 cells was conducted. For comparison, the Janus Fe₃O₄‐TiO₂ NPs parent material TiO₂ NPs was also evaluated. Results showed that both Fe₃O₄‐TiO₂ NPs and TiO₂ NPs decreased cell viability and ATP levels when applied in treatment, but increased malonaldehyde (MDA) and reactive oxygen species (ROS) generation. Mitochondria JC‐1 staining assay showed that mitochondrial membrane permeability injury occurred in both NPs treated cells. Cell viability analysis showed that TiO₂ NPs induced slightly higher cytotoxicity than Fe₃O₄‐TiO₂ NPs in HL7702 cells. Western blotting indicated that both TiO₂ NPs and Fe₃O₄‐TiO₂ NPs could induce apoptosis, inflammation, and carcinogenesis related signal protein alterations. Comparatively, Fe₃O₄‐TiO₂ NPs induced higher signal protein expressions than TiO₂ NPs under a high treatment dose. However, under a low dose (6.25 μg/cm²), neither NPs had any significant toxicity on HL7702 cells. In addition, our results suggest both Fe₃O₄‐TiO₂ NPs and TiO₂ NPs could induce oxidative stress and have a potential carcinogenetic effect in vitro. Further studies are needed to elaborate the detailed mechanisms of toxicity induced by a high dose of Fe₃O₄‐TiO₂ NPs.     

The toxicity and distribution of iron oxide–zinc oxide core‐shell nanoparticles in C57BL/6 mice after repeated subcutaneous administration

Therapeutic cancer vaccines promote immune responses by delivering tumour‐specific antigens. Recently, we developed iron oxide (Fe₃O₄)–zinc oxide (ZnO) core‐shell nanoparticles (CSNPs) as carriers for antigen delivery into dendritic cells (DCs), and the CSNPs were injected subcutaneously into C57BL/6 mice to examine the systemic toxicity, tissue distribution and excretion of the CSNPs. The doses injected were 0, 4, 20 and 200 mg kg^–1 weekly for 4 weeks. No significant changes were observed after the CSNPs administration with respect to mortality, clinical observations, body weight, food intake, water consumption, urinalysis, haematology, serum biochemistry,and organ weights. A dose‐dependent increase in granulomatous inflammation was observed at the injection site of the CSNP‐treated animals, but no other histopathological lesions in other organs could be attributed to the CSNPs. The Zn concentration, which is an indicator for CSNPs, was not significantly higher in the sampled tissues, urine, or faeces after the CSNP injection. In contrast, the Zn concentration at the subcutaneous skin of the site injected with the CSNPs increased in a dose‐dependent manner, along with a macroscopic deposition of the CSNPs. The CSNP residue at the injection site resulted in a foreign body response with the appearance of macrophage infiltration, but otherwise did not show any systemic distribution or toxicity at up to 200 mg kg^–1 during this study. In conclusion, CSNPs could be used as good antigen carriers for DC‐based immunotherapy, although further study is needed to completely clear the residue of the CSNPs at the injection site. Copyright © 2015 John Wiley & Sons, Ltd.     

Toxicological evaluation of silver nanoparticles and silver nitrate in rats following 28 days of repeated oral exposure

The increasing application of silver nanoparticles (AgNPs) has been raising concerns about their potential adverse effects to human and the environment. However, the knowledge on the systemic toxicity of AgNPs in mammalian systems is still limited. The present study investigated the toxicity of PVP‐coated AgNPs in rats treated with repeated oral administration, and compared that with equivalent dose of AgNO₃. Specifically, one hundred male and female rats were orally administrated with particulate or ionic forms of silver (Ag) separately at doses of 0.5 and 1 mg kg^?1 body weight daily for 28 days. The results reveal no significant toxic effects of AgNPs and AgNO₃ up to 1 mg kg^?1 body weight, with respect to the body weight, organ weight, food intake, and histopathological examination. Ag distribution pattern in organs of rats treated with AgNPs was similar to that of AgNO₃ treated rats, showing liver and kidneys are the main target organs followed by testis and spleen. The total Ag contents in organs were significantly lower in the AgNPs treated rats than those in the AgNO₃ treated rats. However, the comparisons between AgNPs and AgNO₃ treatments further indicated more potent of AgNPs in biochemical and hematological parameters in rats, including red blood cell count (RBC), platelet count (PLT), white blood cell count (WBC) and aspartate transaminase (AST). Results of this study suggested that particulate Ag at least partially contributed to the observed toxicity of AgNPs, and both ionic and particulate Ag should be taken into consideration in toxicological evaluation of AgNPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 609–618, 2017.     

Assessment of genotoxicity and biodistribution of nano‐ and micron‐sized yttrium oxide in rats after acute oral treatment

The increasing use of yttrium oxide (Y₂O₃) nanoparticles (NPs) entails an improved understanding of their potential impact on the environmental and human health. In the present study, the acute oral toxicity of Y₂O₃ NPs and their microparticles (MPs) was carried out in female albino Wistar rats with 250, 500 and 1000 mg kg⁻¹ body weight doses. Before the genotoxicity evaluation, characterization of the particles by transmission electron microscopy, dynamic light scattering and laser Doppler velocimetry was performed. The genotoxicity studies were conducted using micronucleus and comet assays. Results showed that Y₂O₃ NP‐induced significant DNA damage at higher dose (1000 mg kg⁻¹ body weight) in peripheral blood leukocytes and liver cells, micronucleus formation in bone marrow and peripheral blood cells. The findings from biochemical assays depicted significant alterations in aspartate transaminase, alanine transaminase, alkaline phosphatase, malondialdehyde, superoxide dismutase, reduced glutathione, catalase and lactate dehydrogenase levels in serum, liver and kidneys at the higher dose only. Furthermore, tissue biodistribution of both particles was analyzed by inductively coupled plasma optical emission spectrometry. Bioaccumulation of yttrium (Y) in all tissues was significant and dose‐, time‐ and organ‐dependent. Moreover, Y₂O₃ NP‐treated rats exhibited higher tissue distribution along with greater clearance through urine whereas Y₂O₃ MP‐dosed animals depicted the maximum amount of Y in the feces. Hence, the results indicated that bioaccumulation of Y₂O₃ NPs via its Y ions may induce genotoxic effects.     

Toxicity assessment of manganese oxide micro and nanoparticles in Wistar rats after 28 days of repeated oral exposure

In the near future, nanotechnology is envisaged for large‐scale use. Hence health and safety issues of nanoparticles (NPs) should be promptly addressed. Twenty‐eight‐day oral toxicity, genotoxicity, biochemical alterations, histopathological changes and tissue distribution of nano and microparticles (MPs) of manganese oxide (MnO₂) in Wistar rats was studied. Genotoxicity was assessed using comet, micronucleus and chromosomal aberration assays. The results demonstrated a significant increase in DNA damage in leukocytes, micronuclei and chromosomal aberrations in bone marrow cells after exposure of MnO₂‐NPs at 1000, 300 mg kg^–1 bw per day and MnO₂‐MPs at the dose of 1000 mg kg^–1 bw per day. Our findings showed acetylcholinestrase inhibition at 1000 as well as at 300 mg kg^–1 bw per day in blood and with all the doses in the brain indicating the toxicity of MnO₂‐NPs. Further, the doses significantly inhibited different ATPases in the brain P₂ fraction. Significant changes were observed in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) in the liver, kidney and serum in a dose‐dependent manner. MnO₂‐MPs at 1000 mg kg^–1 bw per day were found to induce significant alterations in biochemical enzymes. A significant distribution was found in all the tissues in a dose‐dependent manner. MnO₂‐NPs showed a much higher absorptivity and tissue distribution as compared with MnO₂‐MPs. A large fraction of MnO₂‐NPs and MnO₂‐MPs was cleared by urine and feces. Histopathological analysis revealed that MnO₂‐NPs caused alterations in liver, spleen, kidney and brain. The MnO₂‐NPs induced toxicity at lower doses compared with MnO₂‐MPs. Further, this study did not display gender differences after exposure to MnO₂‐NPs and MnO₂‐MPs. Therefore, the results suggested that prolonged exposure to MnO₂ has the potential to cause genetic damage, biochemical alterations and histological changes. Copyright © 2013 John Wiley & Sons, Ltd.     

Microglial activation, recruitment and phagocytosis as linked phenomena in ferric oxide nanoparticle exposure

Microglia as the resident macrophage-like cells in the central nervous system (CNS) play a pivotal role in the innate immune responses of CNS. Understanding the reactions of microglia cells to nanoparticle exposure is important in the exploration of neurobiology of nanoparticles. Here we provide a systemic mapping of microglia and the corresponding pathological changes in olfactory-transport related brain areas of mice with Fe₂O₃-nanoparticle intranasal treatment. We showed that intranasal exposure of Fe₂O₃ nanoparticle could lead to pathological alteration in olfactory bulb, hippocampus and striatum, and caused microglial proliferation, activation and recruitment in these areas, especially in olfactory bulb. Further experiments with BV2 microglial cells showed the exposure to Fe₂O₃ nanoparticles could induce cells proliferation, phagocytosis and generation of ROS and NO, but did not cause significant release of inflammatory factors, including IL-1β, IL-6 and TNF-α. Our results indicate that microglial activation may act as an alarm and defense system in the processes of the exogenous nanoparticles invading and storage in brain.     

Body distribution of SiO2–Fe3O4 core-shell nanoparticles after intravenous injection and intratracheal instillation

Nano-silicon dioxide (SiO₂) is used nowadays in several biomedical applications such as drug delivery and cancer therapy, and is produced on an industrial scale as additive to paints and coatings, cosmetics and food. Data regarding the long-term biokinetics of SiO₂ engineered nanoparticles (ENPs) is lacking. In this study, the whole-body biodistribution of SiO₂ core-shell ENPs containing a paramagnetic core of Fe₃O₄ was investigated after a single exposure via intravenous injection or intratracheal instillation in mice. The distribution and accumulation in different organs was evaluated for a period of 84 days using several techniques, including magnetic resonance imaging, inductively coupled plasma mass spectrometry, X-ray fluorescence and X-ray absorption near edge structure spectroscopy. We demonstrated that intravenously administered SiO₂ ENPs mainly accumulate in the liver, and are retained in this tissue for over 84 days. After intratracheal instillation, an almost complete particle clearance from the lung was seen after 84 days with distribution to spleen and kidney. Furthermore, we have strong evidence that the ENPs retain their original core-shell structure during the whole observation period. This work gives an insight into the whole-body biodistribution of SiO₂ ENPs and will provide guidance for further toxicity studies.     

Changing the dose metric for inhalation toxicity studies: Short-term study in rats with engineered aerosolized amorphous silica nanoparticles

Inhalation toxicity and exposure assessment studies for nonfibrous particulates have traditionally been conducted using particle mass measurements as the preferred dose metric (i.e., mg or μg/m³). However, currently there is a debate regarding the appropriate dose metric for nanoparticle exposure assessment studies in the workplace. The objectives of this study were to characterize aerosol exposures and toxicity in rats of freshly generated amorphous silica (AS) nanoparticles using particle number dose metrics (3.7?×?10⁷ or 1.8?×?10⁸ particles/cm³) for 1- or 3-day exposures. In addition, the role of particle size (d₅₀?=?37 or 83?nm) on pulmonary toxicity and genotoxicity endpoints was assessed at several postexposure time points. A nanoparticle reactor capable of producing, de novo synthesized, aerosolized amorphous silica nanoparticles for inhalation toxicity studies was developed for this study. SiO₂ aerosol nanoparticle synthesis occurred via thermal decomposition of tetraethylorthosilicate (TEOS). The reactor was designed to produce aerosolized nanoparticles at two different particle size ranges, namely d₅₀?=?～30?nm and d₅₀?=?～80?nm; at particle concentrations ranging from 10⁷ to 10⁸ particles/cm³. AS particle aerosol concentrations were consistently generated by the reactor. One- or 3-day aerosol exposures produced no significant pulmonary inflammatory, genotoxic, or adverse lung histopathological effects in rats exposed to very high particle numbers corresponding to a range of mass concentrations (1.8 or 86?mg/m³). Although the present study was a short-term effort, the methodology described herein can be utilized for longer-term inhalation toxicity studies in rats such as 28-day or 90-day studies. The expansion of the concept to subchronic studies is practical, due, in part, to the consistency of the nanoparticle generation method.     

Copper oxide nanoparticles induce oxidative stress and cytotoxicity in airway epithelial cells

Metal oxide nanoparticles are often used as industrial catalysts and elevated levels of these particles have been clearly demonstrated at sites surrounding factories. To date, limited toxicity data on metal oxide nanoparticles are available. To understand the impact of these airborne pollutants on the respiratory system, airway epithelial (HEp-2) cells were exposed to increasing doses of silicon oxide (SiO₂), ferric oxide (Fe₂O₃) and copper oxide (CuO) nanoparticles, the leading metal oxides found in ambient air surrounding factories. CuO induced the greatest amount of cytotoxicity in a dose-dependent manner; while even high doses (400 μg/cm²) of SiO₂ and Fe₂O₃ were non-toxic to HEp-2 cells. Although all metal oxide nanoparticles were able to generate ROS in HEp-2 cells, CuO was better able to overwhelm antioxidant defenses (e.g. catalase and glutathione reductase). A significant increase in the level of 8-isoprostanes and in the ratio of GSSG to total glutathione in cells exposed to CuO suggested that ROS generated by CuO induced oxidative stress in HEp-2 cells. Co-treatment of cells with CuO and the antioxidant resveratrol increased cell viability suggesting that oxidative stress may be the cause of the cytotoxic effect of CuO. These studies demonstrated that there is a high degree of variability in the cytotoxic effects of metal oxides, that this variability is not due to the solubility of the transition metal, and that this variability appears to involve sustained oxidative stress possibly due to redox cycling.     

Berberine‐loaded Janus nanocarriers for magnetic field‐enhanced therapy against hepatocellular carcinoma

Berberine, an bioactive isoquinolin alkaloid from traditional Chinese herbs, is considered to be a promising agent based on its remarkable activity against hepatocellular carcinoma. However, the clinical application of this nature compound had been hampered owing to its properties such as poor aqueous solubility, low gastrointestinal absorption, and reduced bioavailability. Therefore, we developed Janus magnetic mesoporous silica nanoparticles (Fe₃O₄‐mSiO₂ NPs) consisting of a Fe₃O₄ head for magnetic targeting and a mesoporous SiO₂ body for berberine delivery. A pH‐sensitive group was introduced on the surface of mesoporous silica for berberine loading to develop a tumor microenvironment‐responsive nanocarrier, which exhibited uniform morphology, good superparamagnetic properties, high drug‐loading amounts, superior endocytic ability, and low cytotoxicity. Berberine‐loaded Fe₃O₄‐mSiO₂ NPs exerted extraordinarily high specificity for hepatocellular carcinoma cells, which was due to the pH‐responsive berberine release, as well as higher endocytosis capacity in hepatocellular carcinoma cells rather than normal liver cells. More importantly, an external magnetic field could significantly improve antitumor activity of Ber‐loaded Fe₃O₄‐mSiO₂ NPs through enhancing berberine internalization. Taken together, our results suggest that Janus nanocarriers driven by the magnetic field may provide an effective and safe way to facilitate clinical use of berberine against hepatocellular carcinoma.     

A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent

Purpose

Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent.

Methods

In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe₃O₄@OA NPs. The stability and anti phagocytosis of Fe₃O₄@OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo.

Results

These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe₃O₄@OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe₃O₄@OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose.

Conclusions

The DG can validly enhance the tumor-targetting effect of Fe₃O₄@OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

     

Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats

This study investigated the oxidative stress induced after acute oral treatment with 500, 1000 and 2000 mg kg^?1 doses of Al₂O₃‐30 and ?40 nm and bulk Al₂O₃ in Wistar rats. Both the nanomaterials induced significant oxidative stress in a dose‐dependent manner in comparison to the bulk. There was no significant difference between the two nanomaterials. However, the effect decreased with increase with time after treatment. The histopathological examination showed lesions only in liver with Al₂O₃ nanomaterials at 2000 mg kg^?1. Copyright © 2011 John Wiley & Sons, Ltd.     

Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice

The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe₂O₃‐NPs) could be toxic to mice testis. Fe₂O₃‐NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe₂O₃‐NPs have the ability to cross the blood‐testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe₂O₃‐NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe₂O₃‐NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants—superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved‐caspase‐3, and cleaved‐PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe₂O₃‐NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe₂O₃‐NPs treatment. The data from our study entailed that testicular toxicity caused by Fe₂O₃‐NPs exposure may be associated with Fe₂O₃‐NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe₂O₃‐NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe₂O₃‐NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594–608, 2017.     

Fe3O4 nanoparticle redox system modulation via cell‐cycle progression and gene expression in human mesenchymal stem cells

The use of engineered nanoparticles (NPs) across multiple fields and applications has rapidly increased over the last decade owing to their unusual properties. However, there is an increased need in understanding their toxicological effect on human health. Particularly, iron oxide (Fe₃O₄) have been used in various sectors, including biomedical, food, and agriculture, but the current understanding of their impact on human health is inadequate. In this investigation, we assessed the toxic effect of Fe₃O₄ NPs on human mesenchymal stem cells (hMSCs) adopting cell viability, cellular morphological changes, mitochondrial transmembrane potential, and cell‐cycle progression assessment methodologies. Furthermore, the expression of oxidative stress, cell death, and cell‐cycle regulatory genes was assessed using quantitative polymerase chain reaction. The Fe₃O₄ NPs induced cytotoxicity and nuclear morphological changes in hMSCs by dose and time exposure. Cell‐cycle analysis indicated that Fe₃O₄ NPs altered the cell‐cycle progression through a decrease in the proportion of cells in the G₀–G₁ phase. The hMSC mitochondrial membrane potential loss increased with an increase in the concentration of Fe₃O₄ NPs exposure. The observed expression levels of the CYP1A, TNF3, TNFSF10, E2F1, and CCNC genes were significantly upregulated in hMSCs in response to Fe₃O₄ NPs exposure. Our findings suggest that Fe₃O₄ NPs caused metabolic stress through altered cell cycle, oxidative stress, and cell death regulatory gene expression in hMSCs. The results of this investigation revealed that Fe₃O₄ NPs exhibited moderate toxicity on hMSCs and that Fe₃O₄ NPs may have biomedical applications at low concentrations. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 901–912, 2016.     

Facile Synthesis of Core–shell Magnetic Mesoporous Silica Nanoparticles for pH‐sensitive Anticancer Drug Delivery

The facile synthesis of core–shell magnetic mesoporous silica nanoparticles (Fe₃O₄@mSiO₂ NPs) was reported in aqueous phase using cetyltrimethylammonium bromide as a template under alcohol‐free conditions. Compared to the conventional synthesis method for core–shell Fe₃O₄@mSiO₂ NPs, the approach in this study is rapid (only 5‐min reaction time), cheap (without using organic agents), and environmentally friendly (one‐step synthesis in alcohol‐free medium). Doxorubicin (DOX)‐loaded Fe₃O₄@mSiO₂ NPs exert extraordinarily high specificity for liver cancer cells, which was due to the pH‐sensitive doxorubicin release, as well as higher endocytosis capacity in liver cancer cells rather than normal liver cells. The potential advantages of using such Fe₃O₄@mSiO₂ NPs as the vehicle of anticancer drugs were that the Fe₃O₄@mSiO₂ NPs exhibit good biocompatibility, high loading and protection of the guest molecules, selective killing effect, and efficient cellular uptake. The exciting pH‐dependent release properties of doxorubicin‐loaded Fe₃O₄@mSiO₂ NPs make their use a promising strategy for enhancing efficient therapy toward tumors, while reducing the cytotoxicity of doxorubicin to human normal neutral tissue or cells.     

Comparison of toxicity of different nanorod‐type TiO2 polymorphs in vivo and in vitro

It is predicted that the toxicity of nanoparticles may be different depending on the properties of the nanoparticles and biological system being tested. However, the factors that influence the toxicity of nanoparticles have not been adequately investigated. In this study, we characterized two types of TiO₂ nanorods, anatase (ATO) and brookite (BTO), and compared their toxicity in vivo and in vitro. ATO and BTO differed from each other most notably in their surface areas. Treatment with the two TiO₂ nanorods (10 µg ml^–1) produced similar effects on the cell cycle in eight cell lines which are derived from potential target organs of nanoparticles, with the BTO eliciting stronger responses than ATO in all cell lines, among the cell lines, H9C2 showed the maximal change. Similarly, when mice were exposed to two TiO₂ nanorods (1 mg kg^–1), BTO induced clearer histopathological lesions and triggered a more robust secretion of inflammatory cytokines than ATO. Furthermore, we compared the cellular response of both TiO₂ nanorods using BEAS‐2B cells, the human bronchial epithelial cell line. Both nanorods induced cell death by increasing the formation of autophagosome‐like vacuoles. The mitochondrial calcium concentration decreased by exposure of both types, but the distribution of lysosome and endoplasmic reticulum (ER) showed a clear difference between the two nanorods. Thus, we conclude that the surface area acts as an important factor which depends on toxicity of nanorod type‐TiO₂ nanoparticles. Furthermore, the toxicity of nanoparticles varies according to the type of cells tested, and that the assembly of autophagosome‐like vacuoles is a critical part of the cellular response to nanoparticle exposure. Copyright © 2013 John Wiley & Sons, Ltd.     

Biochemical alterations induced by acute oral doses of iron oxide nanoparticles in Wistar rats

Magnetic iron oxide nanoparticles with appropriate surface chemistry have been widely used with potential new applications in biomedical industry. Therefore, the aim of this study was to assess the size-, dose-, and time-dependent effects, after acute oral exposure to iron oxide-30 NP (Fe₂O₃-30), on various biochemical enzyme activities of clinical significances in a female Wistar rat model. Rats were exposed to three different doses (500, 1,000, and 2,000?mg/kg) of Fe₂O₃-30 and Fe₂O₃-Bulk along with control. Fe₂O₃-30 had no effect on growth, behavior, and nutritional performance of animals. Fe₂O₃-30 caused significant inhibition of acetylcholinestrase in red blood cells as well as in brains of treated rats. Further, more than 50% inhibition of total, Na⁺-K⁺, Mg²⁺, and Ca²⁺-ATPases activities, as observed in brains of exposed female rats, may be the result of disturbances in cellular physiology and the iono-regulatory process. Activation of the hepatotoxicity marker enzymes, aspartate aminotransferase and alanine aminotransferase, was recorded in serum and liver, whereas inhibition was observed in kidney. Similarly, enhancement of lactate dehydrogenase activity was observed in serum and liver; however, a decrease in enzyme levels was observed in kidneys of Fe₂O₃-30-treated rats. On the other hand, Fe₂O₃-Bulk did not depict any significant changes in these biochemical parameters, and alterations were near to control. Therefore, this study suggests that exposure to nanosize particles at acute doses may cause adverse changes in animal biochemical profiles. The use of the rat model signifies the correlation with the human system.     

Effect of silver nanoparticle surface coating on bioaccumulation and reproductive toxicity in earthworms (Eisenia fetida)

Abstract

The purpose of this study was to investigate the effect of surface coating on the toxicity of silver nanoparticles (Ag NPs) soil. Earthworms (Eisenia fetida) were exposed to AgNO₃ and Ag NPs with similar size ranges coated with either polyvinylpyrrolidone (hydrophilic) or oleic acid (amphiphilic) during a standard sub-chronic reproduction toxicity test. No significant effects on growth or mortality were observed within any of the test treatments. Significant decreases in reproduction were seen in earthworms exposed to AgNO3, (94.21 mg kg^-1) as well as earthworms exposed to Ag NPs with either coating (727.6 mg kg^-1 for oleic acid and 773.3 mg kg^-1 for polyvinylpyrrolidone). The concentrations of Ag NPs at which effects were observed are much higher than predicted concentrations of Ag NPs in sewage sludge amended soils; however, the concentrations at which adverse effects of AgNO₃ were observed are similar to the highest concentrations of Ag presently observed in sewage sludge in the United States. Earthworms accumulated Ag in a concentration-dependent manner from all Ag sources, with more Ag accumulating in tissues from AgNO₃ compared to earthorms exposed to equivalent concentrations of Ag NPs. No differences were observed in Ag accumulation or toxicity between earthworms exposed to Ag NPs with polyvinylpyrrolidone or oleic acid coatings.     

Nanoecotoxicology study of the response of magnetic O-Carboxymethylchitosan loaded silver nanoparticles on Artemia salina

Magnetic silver nanoparticles (MNPAg) are interesting nanotechnology materials with borderless environmental science, that can be used to disinfect water contaminated with pathogenic bacteria. The use of MNPAg leads to increased risk of nanomaterial contamination in the environment, especially natural water sources, with harmful effects on the ecosystem. This study investigating survival and enzyme activity of magnetic O-carboxymethylchitosan loaded silver nanoparticle on Artemia salina. The results showed that mortality increased with increasing concentrations of MNPAg. O-Carboxymethylchitosan loaded silver nanoparticles were found to be more toxic, with a LC₅₀ of 902.1 mg/L for γ-Fe₂O₃/Ag without reducing agent. Accumulation of silver on Artemia salina depends on the type of nanoparticle. Accumulation of nanoparticle containing polymers (carboxymethylchitosan/γ-Fe₂O₃/Ag without reducing agent, carboxymethylchitosan/γ-Fe₂O₃/Ag reduced with sucrose and carboxymethylchitosan/γ-Fe₂O₃/Ag reduced with NaBH₄) were found to be higher than γ-Fe₂O₃/Ag reduced with NaBH₄, γ-Fe₂O₃/Ag reduced with sucrose and γ-Fe₂O₃/Ag without reducing agent under the same experimental conditions. The antioxidant enzyme (CAT, SOD and GST) activities increased slightly following exposure, indicating that the toxic effects are related to oxidative stress. The combined results so far indicate that MNPA does not have the potential to affect aquatic organisms when released into the ecosystem.