Nanotoxicology最新文献

The role of surfactant proteins A and D (SP-A and SP-D) in lung clearance and translocation to secondary organs of inhaled nanoparticles was investigated by exposing SP-A and SP-D knockout (AKO and DKO) and wild type (WT) mice nose-only for 3 hours to an aerosol of 20 nm gold nanoparticles (AuNPs). Animals were euthanised at 0-, 1-, 7- and 28-days post-exposure. Analysis by inductively coupled plasma mass spectrometry (ICP-MS) of the liver and kidneys showed that extrapulmonary translocation was below the limits of detection. Imaging of the lungs by laser ablation ICP-MS confirmed the homogenous distribution of AuNPs. Coherent anti-Stokes Raman Scattering, Second Harmonic Generation and Two-Photon Fluorescence imaging were applied for semi-quantitative analysis of the uptake of AuNPs by alveolar macrophages and found uptake increased with time post-exposure, peaking after 7 days, and with the largest increase in uptake being in WT mice. Single particle ICP-MS allowed particle counting and sizing of AuNPs in the lungs showing that particle agglomeration following deposition within the lung was greater for the wildtype than the knockout models, indicating a role for SP-A and SP-D in agglomeration, however, any effect of this on overall lung clearance was minimal. For all groups, the Au (mass) lung burden initial clearance half-time was approximately 20-25 d, however, the AuNP (particle number) lung burden clearance half-time was shorter at approximately 10 days. In general terms, differences between the results for the three models were limited, indicating the preferential clearance of smaller particles from the lung.

Toxicity associated with elevated levels of cobalt-chromium-molybdenum (CoCrMo) nanoparticles in total hip replacement (THR) patients has been a rising concern. Recent investigations demonstrated that these particles can induce polyneuropathy in THR patients. The current study aims to address a detailed molecular investigation of CoCrMo nanoparticle-mediated mitochondrial dynamics using induced pluripotent stem cell-derived neurons (iPSC neurons). Telencephalic neurons from iPSCs were used in this study. A statistically significant dose-dependent reduction in membrane potential and mitochondrial superoxide generation was observed after CoCrMo nanoparticle treatment. The gene expression analysis confirmed that the oxidative-specific genes were significantly upregulated in particle-treated cells compared to untreated cells. When iPSCs were exposed to CoCrMo nanoparticles, there was a significant reduction in the area, perimeter, and length of mitochondria. Live cell imaging (mitochondrial tracking) revealed a significant reduction in mitochondrial movements in the presence of CoCrMo nanoparticles. Further protein expression confirmed increased mitochondrial fission in CoCrMo particle-treated cells by significantly upregulating Drp-1 protein and downregulating Mfn-2. In conclusion, the results show that CoCrMo nanoparticles can significantly alter neuronal mitochondrial dynamics. The disturbance in balance restricts mitochondrial movement, reduces energy production, increases oxidative stress, and can cause subsequent neurodegeneration.

The present study rigorously examined the toxicological effects of nanoparticles (NPs), specifically nickel (Ni) and chromium oxide (Cr₃O₄) NPs, synthesized under controlled conditions and characterized. To evaluate their potential environmental impact exposed the freshwater fish Labeo rohita (L. rohita) to environmentally relevant concentrations of both NPs within a controlled laboratory conditions. Vital organs, including gills and liver were subjected to histopathological analysis, revealing profound alterations in tissue architecture that were distinctly correlated with pathological damage. The lesions exhibited moderate to severe changes that are further correlated with the semi-quantitative mean alteration value (MAV). Furthermore, conducted a quantitative assessment of tissue-specific morphological changes. Notably, there was a significant reduction in critical hematological changes, including red blood cell (RBC) and white blood cell (WBC) counts, hemoglobin concentrations and other parameters. All of which exhibited significant fluctuations in relation to increasing NPs concentrations. These findings underscore the critical necessity for continued investigation into the ecological risks associated with these nanoparticles.

Silver nanoparticles (AgNPs) have gained attention in medicine for their potent antibacterial, antiviral, and anti-inflammatory properties. The use of silver nanoparticles in ophthalmic solutions raises concerns regarding potential toxicity of nanoparticles to ocular tissues, such as the cornea, conjunctiva, and retina, which necessitates further toxicity assessments aiding in the development of safer ophthalmic solutions. This study investigates the impact of AgNPs on corneal tissue using ophthalmic investigations, Fourier transform infrared (FTIR) spectroscopy, and chemometric analyses. Three concentrations of AgNPs (0.48 µg/mL, 7.2 µg/mL, and 15.5 µg/mL) were topically applied twice daily for 10 days, synthesized biologically by reducing silver nitrate with almond kernels water extract. Corneas, obtained by cutting 2-3 mm below the ora serrata, were analyzed with FTIR spectroscopy and subjected to chemometric analyses. Results reveal AgNPs' influence on constituents with OH and NH groups, affecting corneal lipids and reducing the lipid saturation index. AgNPs alter both bulk and interfacial water, leading to changes in corneal hydration thus modifying corneal physico-chemical properties. The influence extends to the water environment around proteins and lipids, releasing bound water from phospholipids and disrupting hydrogen bonding networks around proteins. In conclusion, the applied AgNPs concentrations can be linked to dry eye onset.

Understanding the biokinetics of nanoparticles will support the identification of target organs for toxicological endpoints. We investigated the biokinetics of poorly soluble nanomaterials carbon black, multi-walled carbon nanotubes (MWCNT), cerium oxide (CeO₂), titanium dioxide (TiO₂), crystalline silica (SiO₂) in inhalation studies in rodents (the soluble amorphous silica was also included). By reviewing research papers on the inhalation of these substances, we collected physico-chemical data and elemental distribution to organs, urine, and feces. Carbon black, MWCNT, cerium, and titanium accumulated during exposure and persisted in the lung post-exposure (still present at >3000 h). For silica, the amorphous form resulted in silicon accumulation in the lungs. Silicon was increased in the blood. Lymph node accumulation was observed for MWCNT, cerium, and titanium. Liver accumulation was observed for cerium and titanium. Cerium and silicon were increased in the spleen. Titanium accumulated and remained in the spleen (>4000 h). MWCNT were increased in several organs, some of which had a persistent presence of this material. In conclusion, we collected data on the biodistribution of five nanomaterials that, except for amorphous silica, are poorly soluble. The poorly soluble materials or their elements were persistent in the lungs but also showed persistence in other organs. In addition, the data on lung content supports Haber's rule, with titanium being deposited to a greater extent at exposure end than the other materials. Lung deposition seems relatively linear for the collected MMAD values, indicating size may be less important than previously suggested regarding alveolar deposition of the sub-2-micrometer size.

Successful implementation of Safe and Sustainable by Design (SSbD) and grouping approaches requires simple, reliable, and cost-effective assays to facilitate hazard screening at early stages of product development. Especially for nanomaterials (NMs), which exist in many different forms, efficient hazard screening is of utmost importance. Oxidative potential (OP), which is the ability of a substance to induce reactive oxygen species (ROS), is an important indicator of the potential to induce oxidative damage and oxidative stress. A frequently used assay to measure OP of NMs is the ferric reducing ability of serum (FRAS) assay. Although the widely used cuvette-based FRAS protocol is considered a robust assay, its low throughput makes the screening of multiple materials challenging. Here, we adapt the original cuvette-based FRAS assay protocol, into a 96-well format and thereby improve its user-friendliness, simplicity, and screening capacity. The adapted protocol allows for the screening of multiple NMs per plate, and multiple plates per day, where the original protocol allows for the screening of one NM dose-range per day. When comparing the two protocols, the adapted protocol showed slightly decreased assay precision as compared to the original protocol. The results obtained with the adapted protocol were compared using eight reference NMs in an interlaboratory study and showed acceptably low intra- and interlaboratory variation. We conclude that the adapted FRAS assay protocol is suitable to be used for hazard screening to facilitate SSbD and grouping approaches.

Carbon nanomaterials have been widely applied for cutting edge therapeutic applications as they offer tunable physio-chemical properties with economic scale-up options. Nuclear delivery of cancer drugs has been of prime focus since it controls important cellular signaling functions leading to greater anti-cancer drug efficacies. Better cellular drug uptake per unit drug injection drastically reduces severe side-effects of cancer therapies. Similarly, carbon dots (CDs) uptaken by the nucleus can also be used to set-up cutting edge nano delivery systems. In an earlier paper, we showed the cellular uptake and plasma membrane impact of combustion generated yellow luminescing CDs produced by our group from fuel rich combustion reactors in a one-step tunable production. In this paper, we aim to specifically study the nucleus by establishing the uptake kinetics of these combustion-generated yellow luminescing CDs. At sub-lethal doses, after crossing the plasma membrane, they impact the actin and microtubule mesh, affecting cell adhesion and migration; enter nucleus by diffusion processes; modify the overall appearance of the nucleus in terms of morphology; and alter chromatin condensation. We thus establish how this one-step produced, cost and bulk production friendly carbon dots from fuel rich combustion flames can be innovatively repurposed as potential nano delivery agents in cancer cells.

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.