Nanotoxicology最新文献

Urotropine, an antibacterial agent to treat urinary tract bacterial infections, can be also considered as a repurposed drug with formaldehyde-mediated anticancer activity. Recently, we have synthesized urotropine surface modified iron oxide nanoparticles (URO@Fe₃O₄ NPs) with improved colloidal stability and limited cytotoxicity against human fibroblasts. In the present study, we have investigated URO@Fe₃O₄ NP-mediated responses in a panel of forty phenotypically different breast cancer cell lines along with three non-cancerous corresponding cell lines. URO@Fe₃O₄ NPs promoted oxidative stress and FOXO3a-based antioxidant response in breast cancer cells. Elevated levels of GPX4 and decreased levels of ACSL4 in URO@Fe₃O₄ NP-treated breast cancer cells protected against ferroptotic cell death. On the contrary, URO@Fe₃O₄ NPs impaired the activity of PERK, a part of unfolded protein response (UPR), especially when the glucose supply was limited, that was accompanied by genetic instability, and apoptotic and/or necrotic cell death in breast cancer cells. In conclusion, this is the first comprehensive analysis of anticancer effects of URO@Fe₃O₄ NPs against a panel of forty breast cancer cell lines with different receptor status and in glucose replete and deplete conditions. We suggest that presented results might be helpful for designing new nano-based anti-breast cancer strategies.

In this study, we investigated the cytotoxic effect of highly soluble dextran-coated CeO₂ nanoparticles on human fetal lung fibroblasts MRC-5. We examined individual nanoparticle-treated cells by Raman spectroscopy and analyzed Raman spectra using non-negative principal component analysis and k-means clustering. In this way, we determined dose-dependent differences between treated cells, which were reflected through the intensity change of lipid, phospholipid and RNA-related Raman modes. Performing standard biological tests for cell growth, viability and induction of apoptosis in parallel, these changes were correlated with nanoparticle-induced apoptotic processes. The cells with specific spectral characteristics, referring to non-apoptotic, but possibly autophagic cell death modality, were also detected. Additionally, Raman imaging combined with principal component and vertex component analysis was used to map the spatial distribution of biological molecules in treated and untreated cells. This work provided the description of different resulting states of the treated cells depending on the dextran-coated CeO₂ nanoparticles dose, which can be later used in the design of the nanoparticles for industrial or medical applications. The wide content of information resulting from single-cell Raman spectroscopy has the potential to detect biochemical changes caused by nanoparticles that would otherwise require a series of expensive and time-consuming standard biological techniques.

The cellular components of the tumor microenvironment (TME) comprise cancer cells and nonmalignant cells including stromal and immune cells. Exosomes are extracellular vesicles secreted by various types of cells that play a crucial role in intercellular communications within TME. The main goal of this study was to elucidate how exosomes of macrophage cells treated with doxorubicin (DOX) and DOX-loaded cyclodextrin-based nanosponges (DOX-CDNSs), affect melanoma cancer cell proliferation. For this aim, the exosomes of the murine macrophage cell line (RAW 264.7) were isolated and characterized after treating the cells with DOX and DOX-CDNSs. The results demonstrated that DOX-CDNSs at a treatment concentration of 1 µg/mL, were nontoxic for macrophages and remarkably toxic against cancer cells. However, DOX was nontoxic for both cell types at the same treatment concentration. DOX and DOX-CDNSs remarkably declined the viability of both cell types at higher concentrations (25 and 50 µg/mL). Intriguingly, the exosomes of DOX-CD-NSs treated macrophages promoted the viability of cancer cells at the treatment concentrations of 1, 20, and 40 µg/mL. While the exosomes of DOX-treated macrophages increased cell viability of cancer cells only at the lowest concentration. In conclusion, this study suggests that utilization of CD-NSs may augment the toxicity of DOX against cancer cells, while it could direct macrophages toward secreting exosomes that favor the growth of cancer cells.

Fullerenes (C₆₀, C₇₀) as carbon nanomaterials can enter the environment through natural processes and anthropogenic activities, while synthetic fullerenes are commonly used in medicine in targeted therapies in association with antibodies, or anticancer and antimicrobial drugs. As the nanoparticles, they can pass through cell membranes and organelles and accumulate in the entire cytoplasm. The red-fluorescent, water-soluble [70]fullerene derivative C₇₀-OMe-ser, which produces reactive oxygen species upon illumination with an appropriate wavelength, passed into the cytoplasm of the middle region in the Drosophila melanogaster digestive system. To determine whether [70]fullerene nanomaterials that produce fluorescence after entering the cell cytoplasm will hurt its homeostasis, it is necessary to investigate the activation of degenerative and possibly regenerative processes. In vivo, studies on the model species D. melanogaster may help to elucidate whether the water-soluble [70]fullerene derivative that produces fluorescence can still be considered among the most promising nanomaterials. The experiment involved feeding insects ad libitum with yeast paste supplemented with 40 µg of fullerenes/mL for 1 week and 1 month. Thus, adult females and males of D. melanogaster were divided into control (CWM, CWF, CMM, and CMF) and experimental groups (FWM, FWF, FMM, and FMF). The quantitative and qualitative analysis enabled the presentation of the effects of the water-soluble [70]fullerene derivatives on cell proliferation and degeneration. Our study presented that [70]fullerene derivative showed a cytoprotective effect and activated cell proliferation. Therefore, we could conclude that analyzed carbon nanomaterials seemed to be safe for the cells into which they have penetrated.

The rapid development of nanotechnology has resulted in the widespread use of nanoparticles (NPs) in various sectors due to their unique properties and diverse applications. However, the increased exposure of humans to NPs raises concerns about their potential negative impact on human health and the environment. The pathways through which NPs exert adverse effects, including inflammation and oxidative stress, are primarily influenced by their size, shape, surface charge, and chemistry, underscoring the critical need to comprehend and alleviate their potential detrimental impacts. In this context, the natural flavonoid quercetin is a promising candidate for counteracting the toxicity induced by NPs due to its anti-inflammatory and antioxidant properties. This review provides an overview of the existing literature on quercetin's protective effects against NPs-induced toxicity, highlighting its therapeutic benefits and mechanisms of action, focusing on its ability to alleviate oxidative stress, inflammation, and cellular damage caused by various types of NPs. Insights from both in vitro and in vivo studies demonstrate the effectiveness of quercetin in preserving cellular function, modulating apoptotic pathways, and maintaining tissue integrity in the presence of NPs. The potential of quercetin as a natural therapeutic agent against NPs-induced toxicity provides valuable insights for safer use of NPs in various daily applications.

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.