Nanotoxicology最新文献

This study proposes a novel multimodal framework for assessing the time-dependent toxicity of iron oxide nanoparticles (SPIONs), aiming to improve in vitro to in vivo extrapolation (IVIVE). The framework integrates experimental data from Caco-2 cells and C. elegans with sequential mathematical modeling and neural network analysis. By accounting for complex, time-dependent processes such as cellular uptake, intracellular transport, and SPION degradation, this approach addresses the unique toxicological profile of nanoparticles. In vitro experiments evaluated cytotoxicity, reactive oxygen species (ROS) production, and antioxidant enzyme expression over 96 hours, revealing strong correlations between nanoparticle uptake, iron levels, oxidative stress, and cell viability. Mathematical models, validated against experimental data, enable the calculation of IC50 values and facilitate interspecies extrapolation. This integrated methodology, achieving an R² > 0.85 for predictive correlations, holds significant promise for reducing reliance on animal testing in future nanotoxicity evaluations.

The objective of the paper was to conduct a thorough statistical meta-analysis of a publicly available database by examining cell membrane damage (CMD), mitochondrial membrane potential (MMP), nuclear size (NS), nuclear intensity (NI), and cell viability (CVV) responses toward nanoparticles. The set of individual 880 and the subset of 630 measurements contained exposure dose, particle diameter, nanoparticle identity (TiO₂, Ag, SiO₂, CeO₂, ZnO, Cu), and cell type (A549, HCT116, HepaRG, HEPG2, RAW264.7) correlated to toxicity markers. The exposure dose was revealed as the most consistent predictor of toxicity across all endpoints, with higher doses significantly influencing toxicity. The compound-specific response was another important factor, where Ag, ZnO, and Cu, were consistently more cytotoxic, while ZnO and Cu correlated to loss of CVV and MMP. Contrary, TiO₂, CeO₂ and SiO₂ displayed partial protective effects, depending on cell context. The effect of particle size was compound- and endpoint-specific, e.g. smaller particles of CeO₂ displayed greater disruption to nuclear architecture (NS, NI) and MMP, while size had minimal effect on CVV for other compounds. HepaRG cells were the most sensitive, specifically from Cu and ZnO, while epithelial lines (e.g. HCT116, HEPG2) showed more complex patterns. Generally, the dose was confirmed as the most impactful predictor, due to consistent and statistically significant effects. Compounds and cell lines were determined as factors of next-highest importance, displaying mixed but significant effects, and the particle size showed lowest effects. These findings highlight the importance of multi-endpoint, multi-cell-type frameworks in nanotoxicology for compound- and cell-specific risk assessments.

Background and aims: Air pollution represents the second most significant global health burden, and existing epidemiological studies have reported that air pollution is harmful to the liver. To comprehensively understand the relationship between air pollution and liver health, this study quantitatively assessed the effects of air pollutants on liver diseases based on published population studies.

Methods and results: 46 papers from PubMed, Cochrane Library, and Web of Science were included in this study. The study we included covered Asia, Europe, and the Americas, mainly from China (23/46), the United States (7/46), and the United Kingdom (3/46). This study has been registered on PROSPERO (CRD42024515689). A WHO-approved risk of bias (ROB) assessment tool specialized for air quality research was applied to evaluate the bias in the included studies. Statistical analyses were performed in R 4.3.2 with fixed/random-effects models (threshold: I²>50%). Effect values (odds ratio [ORs]/weighted mean differences [WMDs]) were standardized per 10 μg/m³ increment, with sensitivity analysis (leave-one-out), and publication bias tests (Begg/Egger) at P < 0.05. The results indicated that each 10 μg/m³ increment in particulate matter 2.5 mum (PM_2.5) was associated with increased levels of aspartate aminotransferase (AST) (3.25%, 95% CI: 0.87-5.68), alanine aminotransferase (ALT) (1.82%, 95% CI: 0.60-3.04), and gamma-glutamyl transferase (GGT) (1.86%, 95% CI: 0.70-3.01); as well as increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD) (OR = 1.32, 95% CI: 1.21-1.44), liver cancer incidence (OR = 1.22, 95% CI: 1.11-1.35), and liver cancer mortality (OR = 1.47, 95% CI: 1.14-1.90). Particulate matter 10 mum (PM₁₀) and nitrogen dioxide (NO₂) exposure also correlated with elevated liver enzymes. The present study has demonstrated that long-term exposure to air pollutants was associated with a higher risk of developing liver diseases in comparison to short-term exposure. The cohort study yielded more statistically significant findings than the cross-sectional study.

Conclusion: The evidence presented in this study suggested that air pollution was associated with an increased risk of liver enzyme abnormality, incidence of MAFLD, as well as incidence and mortality of liver cancer, reminding the public, environmental and clinical experts, to pay attention to the liver health associated with air pollution.

Colloidal silver is marketed as a dietary supplement, despite lacking essential mineral properties, scientific health benefits and potential toxicity. Therefore, we aimed to evaluate the effects of two commercially available colloidal silver formulations, Almacura (AL) and Prata Vida (PV), on the human hepatoma cell line Huh-7. We determined the IC₅₀ values for the AL formulation as 0.69 µg/mL (cell viability by MTT assay), 0.79 µg/mL (cell count via PI/Hoechst nuclear staining), and 0.93 µg/mL (membrane integrity by PI uptake assay). Similarly, the IC50 values for the PV formulation were 0.62 µg/mL (cell viability by MTT assay), 0.86 µg/mL (cell count via PI/Hoechst nuclear staining), and 1.02 µg/mL (membrane integrity by PI uptake assay). We also examined the contributions of the supernatant, enriched in Ag⁺ ions, and the pellet, mainly composed of AgNPs, to cytotoxicity. Using the MTT assay, we found IC50 values of 0.80 µg/mL for AL and 0.85 µg/mL for PV, indicating that the supernatant is the primary driver of the observed cytotoxicity. High-content imaging (HCI) was performed using the Live Cell Painting assay to evaluate dose-response effects, revealing that both formulations showed cellular changes at lower concentrations compared to MTT assays. In conclusion, this study raises important concerns regarding the safety of commercial colloidal silver, highlighting the need for regulatory standards that consider nanoparticle characteristics and their biological interactions.

The effect of non-functionalized polystyrene nanoparticles (PS-NPs) with diameters of 29, 44, and 72 nm on plasmid DNA integrity and the expression of genes involved in the architecture of chromatin was investigated in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with PS-NPs at concentrations ranging from 0.001 to 100 µg/mL for 24 hours. Gene expression profiling was carried out using quantitative real-time PCR for the following genes: those involved in DNA methylation (DNMT1, DNMT3A), DNA demethylation (TET2, TET3), and chromatin remodeling, including histone methylation (EHMT1, EHMT2) and histone deacetylation (HDAC3, HDAC5). Furthermore, the expression of selected epigenetic markers related to histone acetylation and methylation (H3ac, H3K4me3, H3K9me3) at the protein level was examined using Western blotting. To assess the potential direct interaction of PS-NPs with DNA, a plasmid relaxation assay was performed in an extracellular system. The results demonstrated that PS-NPs do not cleave plasmid DNA directly. The gene expression analysis indicated that PS-NPs did not alter the expression of DNMT1, TET2, TET3, EHMT1, EHMT2, HDAC3, or HDAC5 in PBMCs. However, statistically significant changes in the expression of the DNMT3A gene were observed after exposure to 29 nm nanoparticles (p = 0.016, Kruskal-Wallis test), although post hoc comparisons did not reveal significant differences between individual treatment groups, and no clear dose-dependent trend was evident. PS-NPs induced a statistically significant decrease in post-translational histone modifications, specifically H3ac and H3K4me3. These findings suggest that PS-NPs may influence the epigenetic mechanisms involved in the regulation of chromatin architecture.

Multi-walled carbon nanotubes (MWCNTs) are used to reinforce plastics, but recent studies have demonstrated that exposure to MWCNTs via inhalation or intratracheal instillation induced lung cancer in rats. The present study was designed to determine the role of nuclear factor erythroid 2-related factor (Nrf2) in MWCNT-induced inflammatory response in the lung of mice. Anesthetized male Nrf2 null mice and age-matched wild-type mice were exposed once to MWCNTs at either 0, 10, or 20 µg/mouse by pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and lung tissues were collected after 7 days to evaluate pulmonary inflammation. Exposure to MWCNTs significantly increased BALF total cell counts and total protein level in wild-type mice, but not in Nrf2 null mice. MWCNT-exposed wild-type mice showed the significant increases in interleukin (IL)-1β, IL-6, and keratinocyte-derived chemokines (KC) levels in BALF, but these were not seen in BALF of Nrf2 null mice. Exposure to MWCNTs at 10 and 20 μg/mouse for 7 days did not significantly increase oxidative stress in both genotypes, but exposure to MWCNTs increased the levels of IL-1β and caspase-1 only in the lungs of wild-type mice. Our results demonstrate that Nrf2 promotes MWCNT-induced pulmonary inflammation, probably through inflammasome activation.

The deformation and leaching of substances from micro/nanoplastics under biotic and abiotic conditions is an important yet often overlooked issues for the environment and human health. Furthermore, their interaction with biomolecules can result in corona formation and the surface deformation of micro/nanoplastics. However, the interaction between micro/nanoplastics and biomolecules, e.g. pancreatin, and the resulting deformation/leaching mechanisms, as well as their biological impact, remains insufficiently understood. Therefore, this study aims to examine the deformation/leaching processes of micro/nanoplastics due to the action of the pancreatin. The interaction mechanism between micro/nanoplastics and pancreatin was investigated using multi-spectroscopic and molecular docking approaches. The deformation of micro/nanoplastics was tested based on their functional groups and structure, and their leaching into the pancreatin solution was assessed by measuring aromaticity and oxidative inputs. In addition, deformation and leaching effects of micro/nanoplastics on pancreatin were investigated using its structural characteristics (e.g. aromatic side chains, activity, and agglomeration), as well as bacterial toxicity using Escherichia coli (e.g. viability, biofilm, and oxidative stress). The Fluorescence and UV-VIS spectroscopic results, as well as molecular docking simulations, revealed interactions between micro/nanoplastics and pancreatin. Deformation of the micro/nanoplastics was confirmed using higher carbonyl and hydroxyl indices by ATR-FTIR, and removal and introduction signals by ¹H-NMR. The higher aromaticity and oxidative potential of the pancreatin indicated the leaching of chemicals from the micro/nanoplastics. Furthermore, the metabolic and oxidative responses of E. coli exposed to leachates were influenced by the deformation and leaching of micro/nanoplastics, as well as by the structural characteristics of the pancreatin.

Selenite(Se) is a trace mineral that is essential for cardiac health. This study aims to investigate the beneficial effects of Se on cardiomyocyte damage induced by silver nanoparticles (AgNPs) and to explore the underlying protective mechanisms. H9C2 cells were incubated with AgNPs with or without Se . Cell viability, reactive oxygen species (ROS), mitochondrial membrane potential, NAD⁺/NADH ratios, ATP levels, the mTOR signaling pathway, and autophagic proteins were measured. The results showed that AgNPs exposure significantly decreased cell viability, inhibited cell proliferation, and changed cell morphology. AgNPs dramatically elevated ROS production and descended mitochondrial membrane potential. Furthermore, the NAD⁺/NADH ratio and ATP level of the AgNPs exposure group were significantly lower than those of the control group. AgNPs activated AMPK, depressed mTOR, and increased LC3 II/I and P62(P < 0.05). Interestingly, treatment with Se effectively salvaged AgNPs-induced cardiomyocyte damage, reduced ROS accumulation, stabilized mitochondrial membrane potential, restored the NAD⁺/NADH ratio and ATP level, and prevented the activation of mTOR and autophagy dysfunction induced by AgNPs. Se mitigates AgNPs-induced cardiomyocyte damage by utilizing antioxidative properties and suppressing mitochondrial dysfunction mediated autophagy through regulating AMPK/mTOR signaling pathway.

With advances in the application of graphene oxide (GO), the major hindering factor is its toxicity. It is crucial to understand the immediate effects on the parent generation as well as the long-term multigenerational effects on subsequent generations. In this paper we investigated the multigenerational effect of GO from the parent to subsequent generations (F0, F1, F2, F3 to F4) in Drosophila melanogaster model organism. Flies were exposed to GO through the ingestion method at concentrations ranging from 50 µg/mL, 100 µg/mL, and 250 µg/mL. The effects of GO were studied at different levels via climbing assay, longevity assay, oxidative stress and phenotypic screening in subsequent generations. Significant declines were observed in the climbing ability, an increase in oxidative stress (F2), and a decrease in lifespan of the parent (F0) to progeny (F1, F2) flies exposed to GO. Critically, the reversal of these toxic effects in the later generations (F3-F4), suggests the development of adaptive mechanisms through which flies overcome the detrimental impacts of prolonged GO exposure. These findings underscore the importance of examining the multigenerational effects of nanomaterials (NMs), as the initial toxicity may not persist over time due to the emergence of adaptive responses in subsequent generations. Understanding and mitigating the toxicity of GO over generations is essential for its safe application in various fields.

Bone, a complex nanocomposite, has yet to be successfully replicated in a commercially available bone regenerative product that fully recapitulates this dual-phase nanoscale architecture. This study investigated the biocompatibility and safety of a nanoalloplastic composed of spherical nanohydroxyapatite (nHA; 30-45 nm)/tricalcium phosphate (TCP) and osteogenic, angiogenic and immunomodulatory self-assembling peptide nanofibers (15-20 nm), designed to mimic the natural nanocomposite structure of bone. Adhering to ISO 10993 protocols, the nanocomposite was subjected to rigorous biocompatibility evaluation by IFDA laboratories. This assessment encompassed cytotoxicity, genotoxicity, hemocompatibility, sensitization, and irritation, as well as acute and chronic systemic toxicity studies. Results demonstrated the material's non-cytotoxic nature, with no significant reduction in cell viability. Hemocompatibility testing revealed acceptable hemolytic activity, while genotoxicity assays showed no evidence of DNA damage. Neither irritation nor sensitization was observed. Systemic toxicity studies in mice revealed no adverse clinical signs, weight changes, or organ pathologies. Bone regeneration study showed complete and osteoinductive potential over one month in rabbits. The peptide nanofibers contribute to the material's biocompatibility through their ECM-mimicking sequences, nanofibrous architecture, biodegradability, and toxic- and solvent-free nature. TCP and spherical nHA with an optimum particle size, morphology, crystallinity, dissolution rate, and significant pH stability, collectively ensure its biocompatibility and vascularized bone formation. These findings validate the biocompatibility and safety of this osteoinductive nanocomposite. The integration of spherical nHA and self-assembling peptide nanofibers appears to generate a biomimetic microenvironment that improves cellular interactions, thereby accelerating bone regeneration and confirming its biocompatibility, positioning it as a revolutionary solution for bone regeneration.