Nanotoxicology最新文献

Metal-based nanomaterials (MNMs) have gained particular interest in nanotechnology industry. They are used in various industrial processes, in biomedical applications or to improve functional properties of several consumer products. The widescale use of MNMs in the global consumer market has resulted in increases in the likelihood of exposure and risks to human beings. Human exposure to MNMs and assessment of their potential health effects through the concomitant application of biomarkers of exposure and effect of the most commonly used MNMs were reviewed in this paper. In particular, interactions of MNMs with biological systems and the nanobiomonitoring as a prevention tool to detect the early damage caused by MNMs as well as related topics like the influence of some physicochemical features of MNMs and availability of analytical approaches for MNMs testing in human samples were summarized in this review. The studies collected and discussed seek to increase the current knowledge on the internal dose exposure and health effects of MNMs, highlighting the advantages in using biomarkers in primary prevention and health surveillance.

The present study aimed to assess the safety, toxicity, biodistribution, and pharmacokinetics of eugenol nanoparticles (EONs) following oral administration in Wistar rat models. In the acute toxicity study, the rats were given a fixed dose of 50, 300, and 2000 mg/kg body weight per group orally and screened for 2 weeks after administration. In the subacute study, three different doses (500, 1000, and 2000 mg/kg BW) of EON were administered for 28 days. The results indicated no significant differences in food and water consumption, bodyweight change, hematological and biochemical parameters, relative organ weights, gross findings, or histopathology compared to the control. Additionally, no significant changes were observed in the expression profiles of inflammatory cytokines such as IL-1, IL-6, and TNFα in the plasma, confirming the absence of systemic inflammation. Biodistribution analysis revealed rapid absorption of eugenol and improved bioavailability due to gradual and sustained release, leading to a maximum eugenol concentration of 15.05 μg/mL (Cmax) at approximately 8 h (Tmax) in the blood plasma. Thus, the study provides valuable insights into the utilization of EON for enhancing the stability, solubility, and sustained release of eugenol and highlights its promising safety profile in vivo.

Nanotechnology applications in biomedicine have increased in recent decades, primarily as therapeutic agents, drugs, and gene delivery systems. Among the nanoparticles used in medicine, we highlight cationic solid lipid nanoparticles (SLN). Given their nontoxic properties, much research has focused on the beneficial effects of SLN for drug or gene delivery system. However, little attention has been paid to the adverse impacts of SLN on the cellular environment, particularly their influence on intracellular signaling pathways. In this work, we investigate the effects triggered by cationic SLN on human prostate non-tumor cells (PNT1A) and tumor cells (PC-3). Our results demonstrate that cationic SLN enhances the migration of PC-3 prostate cancer cells but not PNT1A non-tumor prostate cells, an unexpected and unprecedented development. Furthermore, we observed that the enhanced cell migration velocity is a concentration-dependent and nanoparticle-dependent effect, and not related to any individual nanoparticle component. Moreover, cationic SLN increased vimentin expression (p < 0.05) but SLN did not affect Smad2 nuclear translocation. Meanwhile, EMT-related (epithelial-to-mesenchymal transition) proteins, such as ZEB1, underwent nuclear translocation when treated with cationic SLN, thereby affecting PC-3 cell motility through ZEB1 and vimentin modulation. From a therapeutic perspective, cationic SLN could potentially worsen a patient's condition if these results were reproduced in vivo. Understanding the in vitro molecular mechanisms triggered by nanomaterials and their implications for cell function is crucial for defining their safe and effective use.

In the lung, carcinogenesis is a multi-stage process that includes initiation by a genotoxic agent, promotion that expands the population of cells with damaged DNA to form a tumor, and progression from benign to malignant neoplasms. We have previously shown that Mitsui-7, a long and rigid multi-walled carbon nanotube (MWCNT), promotes pulmonary carcinogenesis in a mouse model. To investigate the potential exposure threshold and dose-response for tumor promotion by this MWCNT, 3-methylcholanthrene (MC) initiated (10 μg/g, i.p., once) or vehicle (corn oil) treated B6C3F1 mice were exposed by inhalation to filtered air or MWCNT (5 mg/m³) for 5 h/day for 0, 2, 5, or 10 days and were followed for 17 months post-exposure for evidence of lung tumors. Pulmonary neoplasia incidence in MC-initiated mice significantly increased with each MWCNT exposure duration. Exposure to either MC or MWCNT alone did not affect pulmonary neoplasia incidence compared with vehicle controls. Lung tumor multiplicity in MC-initiated mice also significantly increased with each MWCNT exposure duration. Thus, a significantly higher lung tumor multiplicity was observed after a 10-day MWCNT exposure than following a 2-day exposure. Both bronchioloalveolar adenoma and bronchioloalveolar adenocarcinoma multiplicity in MC-initiated mice were significantly increased following 5- and 10-day MWCNT exposure, while a 2-day MWCNT exposure in MC-initiated mice significantly increased the multiplicity of adenomas but not adenocarcinomas. In this study, even the lowest MWCNT exposure promoted lung tumors in MC-initiated mice. Our findings indicate that exposure to this MWCNT strongly promotes pulmonary carcinogenesis.

Assessing research activity is an important step for planning future initiatives oriented toward filling the remaining gaps in a field. Therefore, the objective of the current study was to review recently published research on pulmonary toxicity caused by nanomaterials. However, here, instead of reviewing possible toxic effects and discussing their mode of action, the goal was to establish trends considering for example examined so far nanomaterials or used testing strategies. A total of 2316 related articles retrieved from the three most cited databases (PubMed Scopus, Web of Science), selected based on the title and abstract requirements, were used as the source of the review. Based on the bibliometric analysis, the nano-meter metal oxides, and carbon-based nanotubes were identified as the most frequently studied nanomaterials, while quantum dots, which might induce possible harmful effects, were not considered so far. The majority of testing of pulmonary safety is based on in vitro studies with observed growth of the contribution of novel testing strategies, such as 3D lung model, air-liquid interface system, or omic analysis.

Despite all benefits of nanomaterials, their unique characteristics made them an emerging hazard in workplaces, which need to be assessed for their potential risks. So, the aim of this study was to review all the studies conducted on the risk assessment of activities involving nanomaterials with CB-based methods.This study is based on a literature review on databases including Web of science, Scopus, PubMed, and SID. After reviewing and screening studies according to PRISMA, the collected data were meta-analyzed by Comprehensive Meta-Analysis Software. Also, Newcastle-Ottawa checklist was used for quality assessment of the studies. To determine similarity of methods, Cohen's Kappa was used. Sensitivity analysis was used to determine the role of each factor in the risk assessment by using the Crystal Ball tool.There are eight validated methods for risk assessment. Also, some authors used a self-deigned tool based on CB approach. The results of meta-analysis showed that the odds ratio for the risk of activities involved with nanomaterials was 0.654 (high risk). Results of simulation for Nanotool showed that the mean risk level of activities involved with nanomaterials, with a certainty of 95.07%, is moderate (RL3). Moreover, sensitivity analysis showed that the risk was depended on "Hazard band" in all methods except ISO method.The obtained results can be useful in improving existing methods and suggesting new methods. Also, there is a need to design and propose specific methods for risk assessment of incidental and natural nanomaterials.

Nanocrystal drug formulation involves several critical manufacturing procedures that result in complex structures to improve drug solubility, dissolution, bioavailability, and consequently the efficacy of poorly soluble Biopharmaceutics Classification System (BCS) II and IV drugs. Nanocrystal formulation of an already approved oral drug may need additional immunotoxic assessment due to changes in the physical properties of the active pharmaceutical ingredient (API). In this study, we selected Zileuton, an FDA-approved drug that belongs to BCS-II for nanocrystal formulation. To evaluate the efficacy and mucosal immune profile of the nanocrystal drug, 10-week-old rats were dosed using capsules containing either API alone or nanocrystal formulated Zileuton (NDZ), or with a physical mixture (PM) using flexible oral gavage syringes. Control groups consisted of untreated, or placebo treated animals. Test formulations were administrated to rats at a dose of 30 mg/kg body weight (bw) once a day for 15 days. The rats treated with NDZ or PM had approximately 4.0 times lower (7.5 mg/kg bw) API when compared to the micron sized API treated rats. At the end of treatment, mucosal (intestinal tissue) and circulating cytokines were measured. The immunological response revealed that NDZ decreased several proinflammatory cytokines in the ileal mucosa (Interleukin-18, Tumor necrosis Factor-α and RANTES [regulated upon activation, normal T cell expressed and secreted]). A similar pattern in the cytokine profile was also observed for the micron sized API and PM treated rats. The cytokine production revealed that there was a significant increase in the production of IL-1β and IL-10 in the females in all experimental groups. Additionally, NDZ showed an immunosuppressive effect on proinflammatory cytokines both locally and systemically, which was similar to the response in micron sized API treated rats. These findings indicate that NDZ significantly decreased several proinflammatory cytokines and it displays less immunotoxicity, probably due to the nanocrystal formulation. Thus, the nanocrystal formulation is more suitable for oral drug delivery, as it exhibited better efficacy, safety, and reduced toxicity.

Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer. In this study, we performed biodistribution and histological analysis of a new IONP (RCL-01) in Wistar rats. These nanoparticles are currently undergoing clinical assessment in locally advanced pancreatic ductal adenocarcinoma to determine the feasibility of magnetic hyperthermia treatment in this disease. The study presented here aimed to determine the fate of these nanoparticles in vivo and whether this results in organ damage. Wistar rats were injected intravenously with relatively high doses of IONP (30 mg_Fe/kg, 45 mg_Fe/kg and 60 mg_Fe/kg) and compared to a vehicle control to determine the accumulation of iron in organs and whether this resulted in histological changes in these tissues. Dose-dependent increases of iron were observed in the liver, spleen and lungs of IONP-treated animals at 7 days postinjection; however, this did not result in significant histological changes in these tissues. Immunofluorescent imaging determined these nanoparticles are internalized by macrophages in tissue, suggesting they are readily phagocytosed by the reticuloendothelial system for eventual recycling. Notably, no changes in iron or dextran staining were found in the kidneys across all treatment groups, providing evidence for potential renal clearance.