Nanotoxicology最新文献

Zinc oxide (ZnO) and nickel oxide (NiO) nanoparticles (NPs) are widely used in various industries due to their distinctive physico-chemical and biological properties. However, concerns have been raised about their potential toxicity in humans. While many studies have reviewed their effects on visceral organs upon ingestion, inhalation, or skin contact, limited reviews are available regarding their adverse consequences on the liver and kidneys resulting from intraperitoneal administration in rats. Hence, this systematic review is the first to uniquely address this issue. A systematic search was performed on PubMed and Google scholar to identify articles that explored the toxic effects of ZnO-NPs and NiO-NPs in rats following intraperitoneal injection. The quality of the articles was assessed using SYCLE's risk of bias tool, leading to the selection of 16 articles; 14 for ZnO-NPs, 1 for NiO-NPs and 1 for both NPs. This review revealed that ZnO-NPs induces an acute toxicity in liver and kidney that is dose dependent. The impairments were marked by changes in organs functional markers, lipid and glucose levels and antioxidant deficiencies and lipid peroxidation. NiO-NPs also showed considerable toxicity, despite the limited studies. Further, variability of physico-chemical properties among studies complicated the toxicity assessment. To conclude, this study provides a novel contribution by summarizing the literature findings that suggest potential adverse intraperitoneal hepatorenal toxic outcomes associated with ZnO-NPs and NiO-NPs. Future research should focus on long-term effects and standardizing protocols to ensure the safe use of ZnO-NPs and NiO-NPs in industrial and clinical practices.

Immunostimulation caused by nanoparticles may be beneficial or adverse depending on their intended application. Activation of immune cells is beneficial for indications targeting the immune system for therapeutic purposes, such as tumor microenvironment reprogramming, immunotherapy, and vaccines. When it is unwanted, however, immunostimulation may lead to excessive inflammation, cytokine storm, and hypersensitivity reactions. The increasing use of silica nanoparticles (SiNPs) for the delivery of drugs, imaging agents, and antigens warrants preclinical studies aimed at understanding carrier-mediated effects on the number, activation status, and function of immune cell subsets. Herein, we present an in vitro study utilizing primary human peripheral blood mononuclear cells (PBMC) to investigate the proinflammatory properties of four types of SiNPs varying in size and porosity. Cytokine analysis was performed in resting and LPS-primed PBMC cultures to understand the ability of silica nanoparticles to induce de novo and exaggerate preexisting inflammation, respectively. Changes in the number and activation status of lymphoid and myeloid cells were studied by flow cytometry to gain further insight into SiNP-mediated immunostimulation. Nonporous SiNPs were found to be more proinflammatory than mesoporous SiNPs, and larger-sized particles induced greater cytokine response. LPS-primed PBMC resulted in increased susceptibility to SiNPs. Immunophenotyping analysis of SiNP-treated PBMC resulted in T and B lymphocyte, natural killer cell, and dendritic cell activation. Additionally, a loss of regulatory T cells and an increase in γδ TCR T cell population were observed with all particles. These findings have implications for the utility of SiNPs for the delivery of drugs and imaging agents.

Silica nanoparticles are increasingly considered for drug delivery applications. These applications require an understanding of their biocompatibility, including their interactions with the immune system. However, systematic studies for silica nanoparticle immunological safety profiles are lacking. To fill this gap, we conducted an in vitro study investigating various aspects of silica nanoparticles' interactions with blood and immune cells. Four types of silica nanoparticles with variations in size and porosity were studied. These included nonporous Stöber silica nanoparticles with average diameters of approximately 50 and 100 nm (SNP50 and SNP100), mesoporous silica nanoparticles of approximately 100 nm (Meso100), and hollow mesoporous silica nanoparticles of approximately 100 nm (HMSNP100) in diameter, respectively. The hematological compatibility was assessed using hemolysis, complement activation, platelet aggregation, and plasma coagulation assays. The effects of nanoparticles on immune cell function were studied using in vitro phagocytosis, chemotaxis, natural killer cell cytotoxicity, leukocyte proliferation, human lymphocyte activation, colony-forming unit granulocyte-macrophage, and leukocyte procoagulant activity assays. The in vitro findings suggest that at high concentrations, corresponding to the in vivo human dose of 40 mg/kg, silica nanoparticles demonstrated an array of immunotoxic effects that depended on their physicochemical properties. However, all types of silica nanoparticles studied were not immunotoxic at concentrations corresponding to lower doses (≤ 8 mg/kg) comparable to that of nanocarriers in other nanomedicines currently used in the clinic. These findings are promising for using silica nanoparticles for the systemic delivery of bioactive and imaging agents.

A critical review of the current state-of-the-science for the physiologically based pharmacokinetic (PBPK) modeling of metal nanoparticles and their application to human health risk assessment for inhalation exposures was conducted. A systematic literature search was used to identify four model groups (defined as a primary publication along with multiple supplementary publications) subject to review. Using a recent guideline document from the Organization for Economic Cooperation and Development (OECD) for PBPK model evaluation, these model groups were critically peer-reviewed by an independent panel of experts to identify those to be considered for modeling and simulation application. Based upon the expert panel input, model confidence scores for the four model groups ranged from 30 to 41 (out of a maximum score of 50). The three highest-scoring model groups were then applied to compare predictions to a different metal nanoparticle (i.e. not specifically used to parameterize the original models) using a recently published data set for tissue burdens in rats, as well as predicting human tissue burdens expected for corresponding occupational exposures. Overall, the rat models performed reasonably well in predicting the lung but tended to overestimate systemic tissue burdens. Data needs for improving the state-of-the-science, including quantitative particle characterization in tissues, nanoparticle-corona data, long-term exposure data, interspecies extrapolation methods, and human biomonitoring/toxicokinetic data are discussed.

Nano-sized titanium dioxide particles (TiO₂ NPs) are a high-production volume nanomaterial widely used in the paints, cosmetics, food and photovoltaics industry. However, the potential carcinogenic effects of TiO₂ NPs in the lung are still unclear despite the vast number of in vitro and in vivo studies investigating TiO₂ NPs. Here, we systematically reviewed the existing in vitro and in vivo mechanistic evidence of TiO₂ NP lung carcinogenicity using the ten key characteristics of carcinogens for identifying and classifying carcinogens. A total of 346 studies qualified for the quality and reliability assessment, of which 206 were considered good quality. Using a weight-of-evidence approach, these studies provided mainly moderate to high confidence for the biological endpoints regarding genotoxicity, oxidative stress and chronic inflammation. A limited number of studies investigated other endpoints important to carcinogenesis, relating to proliferation and transformation, epigenetic alterations and receptor-mediated effects. In summary, TiO₂ NPs might possess the ability to induce chronic inflammation and oxidative stress, but it was challenging to compare the findings in the studies due to the wide variety of TiO₂ NPs differing in their physicochemical characteristics, formulation, exposure scenarios/test systems, and experimental protocols. Given the limited number of high-quality and high-reliability studies identified within this review, there is a lack of good enough mechanistic evidence for TiO₂ NP lung carcinogenicity. Future toxicology/carcinogenicity research must consider including positive controls, endotoxin testing (where necessary), statistical power analysis, and relevant biological endpoints, to improve the study quality and provide reliable data for evaluating TiO₂ NP-induced lung carcinogenicity.

The need of the hour with respect to cancer treatment is a targeted approach with minimal or nil ramifications. Apropos, magnetic fluid hyperthermia (MFH) is emerging as a potential therapeutic strategy with anticipated reduced side effects for solid tumors. MFH causes cytotoxicity due to the heat generated owing to Hysteresis, Neel, and Brownian relaxation losses once magnetic nanoparticles (MNPs) carrying cancer cells are placed under an alternating magnetic field. With respect to MFH, iron oxide-based MNPs have been most extensively studied to date compared to other metal oxides with magnetic properties. The effectiveness of MFH relies on the composition, coating, size, physical and biocompatible properties of the MNPs. Pure iron oxide and doped iron oxide MNPs have been utilized to study their effects on cancer cell killing through MFH. This review evaluates the biocompatibility of pure and doped iron oxide MNPs and their subsequent hyperthermic effect for effectively killing cancer cells in vitro and in vivo.

Polyethylene (PE) is one of the most widely used plastics in the world. Its degradation leads to the production of small particles including microplastics and nanoplastics (NPs). Plastic particles' presence poses a health risk. The aim of this work was to investigate the toxicity of two model surfactant-free PE NPs prepared by polymerization of ethylene from cationic and anionic water-soluble initiators on human cell lines Caco-2 and HT29-MTX. After physicochemical characterization, their acute and subacute toxicity profile, including cytotoxicity, oxidative stress, and genotoxicity, was evaluated on both cell lines. Results showed a size increase of PE NPs in culture medium. Zeta potential values close to -10 mV were no longer dependent on the initiator charge after adsorption of serum components in culture medium. However, the cellular toxicity of the cationic and anionic PE NPs was very different. A time-and-concentration dependent cytotoxic, oxidative, and genotoxic effects on Caco-2 cells were only observed for PE NPs prepared with cationic initiators. No toxicity was observed on HT29-MTX, likely due to the protective mucus layer. Genotoxicity correlated with oxidative stress of some PE NPs on Caco-2 cells was observed from a concentration of 0.1 mg.mL^-1 after 48-h exposure.

Iron oxide nanoparticles (IONPs) have been extensively explored in biomedicine, bio-sensing, hyperthermia, and drug/gene delivery, attributed to their versatile and tunable properties. However, owing to its numerous applications, the functionalization of IONPs with appropriate materials is in demand. To achieve optimal functionalization of IONPs, polydopamine (PDA) was utilized due to its ability to provide a superior functionalized surface, near-infrared light absorption, and adhesive nature to customize desired functionalized IONPs. This notion of involving PDA led to the successful synthesis of magnetite-PDA nanoparticles, where PDA is surface-coated on magnetite (Fe₃O₄@PDA). The Fe₃O₄@PDA nanoparticles were characterized using techniques like TEM, FESEM, PXRD, XPS, VSM, and FTIR, suggesting PDA's successful attachment with magnetite crystal structure retention. Human serum albumin (HSA), the predominant protein in blood plasma, interacts with the delivered nanoparticles. Therefore, we have employed various spectroscopic techniques, along with cytotoxicity, to inspect the effect of Fe₃O₄@PDA NPs on the stability and structure of HSA. The structural alterations were examined using circular dichroism (CD) and synchronous fluorescence spectroscopy (SFS). It has been observed that there are no structural perturbations in the secondary structure of the HSA protein after interaction with Fe₃O₄@PDA. Studies using steady-state fluorescence revealed that the inherent fluorescence intensities of HSA were suppressed after interaction with Fe₃O₄@PDA. In addition, temperature-dependent fluorescence measurements suggested that the type of quenching consists of both static and dynamic quenching simultaneously. A cytotoxicity study in Drosophila melanogaster larvae revealed no cytotoxic effects but did show a minor genotoxic effect only at higher concentrations.