Cytotoxicity and genotoxicity of low-dose vanadium dioxide nanoparticles to lung cells following long-term exposure.

Vanadium dioxide nanoparticles (VO2 NPs) have been massively produced and widely applied due to their excellent metal-insulator transition property, making it extremely urgent to evaluate their safety, especially for low-dose long-term respiratory occupational exposure. Here, we report a comprehensive cytotoxicity and genotoxicity study on VO2 NPs to lung cell lines A549 and BEAS-2B following a long-term exposure. A commercial VO2 NP, S-VO2, was used to treat BEAS-2B (0.15-0.6 µg/mL) and A549 (0.3-1.2 µg/mL) cells for four exposure cycles, and each exposure cycle lasted for 4 consecutive days; then various bioassays were performed after each cycle. Significant proliferation inhibition was observed in both cell lines after long-term exposure of S-VO2 at low doses that did not cause apparent acute cytotoxicity; however, the genotoxicity of S-VO2, characterized by DNA damage and micronuclei, was only observed in A549 cells. These adverse effects of S-VO2 were exposure time-, dose- and cell-dependent, and closely related to the solubility of S-VO2. The oxidative stress in cells, i.e., enhanced reactive oxygen species (ROS) generation and suppressed reduced glutathione, was the main toxicity mechanism of S-VO2. The ROS-associated mitochondrial damage and DNA damage led to the genotoxicity, and cell proliferation retard, resulting in the cellular viability loss. Our results highlight the importance and urgent necessity of the investigation on the long-term toxicity of VO2 NPs.

Effects of VO2 nanoparticles on human liver HepG2 cells: Cytotoxicity, genotoxicity, and glucose and lipid metabolism disorders.

The rapid development of smart materials stimulates the production of vanadium dioxide (VO2) nanomaterials. This significantly increases the population exposure to VO2 nanomaterials via different pathways, and thus urges us to pay more attentions to their biosafety. Liver is the primary accumulation organ of nanomaterials in vivo, but the knowledge of effects of VO2 nanomaterials on the liver is extremely lacking. In this work, we comprehensively evaluated the effects of a commercial VO2 nanoparticle, S-VO2, in a liver cell line HepG2 to illuminate the potential hepatic toxicity of VO2 nanomaterials. The results indicated that S-VO2 was cytotoxic and genotoxic to HepG2 cells, mainly by inhibiting the cell proliferation. Apoptosis was observed at higher dose of S-VO2, while DNA damage was detected at all tested concentrations. S-VO2 particles were internalized by HepG2 cells and kept almost intact inside cells. Both the particle and dissolved species of S-VO2 contributed to the observed toxicities. They induced the overproduction of ROS, and then caused the mitochondrial dysfunction, ATP synthesis interruption, and DNA damages, consequently arrested the cell cycle in G2/M phase and inhibited the proliferation of HepG2 cells. The S-VO2 exposure also resulted in the upregulations of glucose uptake and lipid content in HepG2 cells, which were attributed to the ROS production and autophagy flux block, respectively. Our findings offer valuable insights into the liver toxicity of VO2 nanomaterials, benefiting their safely practical applications.

Cytotoxicity of vanadium oxide nanoparticles and titanium dioxide-coated vanadium oxide nanoparticles to human lung cells.

Due to excellent metal-insulator transition property, vanadium dioxide nanoparticles (VO2 NPs)-based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO2 NPs exposure through various routes. Herein, the cytotoxicity of VO2 NPs (N-VO2 ) and titanium dioxide-coated VO2 NPs (T-VO2 ) to typical human lung cell lines (A549 and BEAS-2B) was studied by using a series of biological assays. It was found that both VO2 NPs induced a dose-dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO2 NPs. Under the same conditions, T-VO2 NPs showed slightly lower cytotoxicity than N-VO2 in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO2 NPs. Titanium dioxide coating changed the surface property of VO2 NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO2 NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase-3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS-2B cells was one of the major mechanisms of the cytotoxicity of VO2 NPs. These findings provide safety guidance for the practical applications of vanadium dioxide-based materials.

Unexpected Size Effect: The Interplay between Different-Sized Nanoparticles in Their Cellular Uptake.

The size effect on the cellular uptake of nanoparticles (NPs) has been extensively studied, but it is still not well understood. Herein, a reductionist approach is used to minimize all influencing factors except the particle size, and co-exposure of different-sized silica nanoparticles (SNPs) is adopted instead of the common single exposure. SNPs are found being internalized by Hela cells in serum-free medium mainly via clathrin-dependent endocytosis, thus simplifying the data analysis for reliable attribution to size effects. Remarkably, even though at conditions that the size effects seem very small or even undetectable in the common single exposure experiments, the co-exposure experiments reveal significant size effects due to an unexpected interplay between two different-sized SNPs. Namely, the bigger SNPs significantly promote the cellular uptake of the smaller ones, while the smaller SNPs inhibit the internalization of the bigger ones, with a total uptake increase of the particle number of SNPs in the cells. This strong interplay between different-sized NPs might unavoidably exist within most "single-sized" NP products, whose sizes actually distribute in certain ranges, thus urging reconsideration of the size effect on the cellular uptake of NPs, for the benefits of both bioapplications and safety assessment of nanomaterials.

Toxicity assessment and mechanistic investigation of engineered monoclinic VO2 nanoparticles.

Growing interest in monoclinic VO2 nanoparticles (NPs) among consumers and the industries of window coatings, solar sensors etc. has brought particular attention to their safety concerns. The toxicity of this new class of nanomaterials in bacterial ecosystems has not yet been evaluated. The degree of crystallinity is a significant parameter that determines the performance of materials. However, the previously reported methods for toxicity assessment have neglected its influence. In this work, we systematically evaluated the toxicity of VO2 NPs with different degrees of crystallinity to four typical bacterial strains and studied the influence of physicochemical properties and aging treatment on their antibacterial effect. The results showed that the toxicity of VO2 nanoparticles was very low. Interestingly, we found that antibacterial properties of VO2 NPs were dependent on both bacterial strains and VO2 particle properties. In addition, the highly crystalline VO2 NPs were more toxic than normal and industrial VO2 particles. We attribute the crystallinity-related toxicity to the dissolved vanadium, the physical interactions between the bacteria and particles, and the generation of reactive oxygen species, as supported by our experimental results and theoretical calculation.

Toxicological Effects of Caco-2 Cells Following Short-Term and Long-Term Exposure to Ag Nanoparticles.

Extensive utilization increases the exposure of humans to Ag nanoparticles (NPs) via the oral pathway. To comprehensively address the action of Ag NPs to the gastrointestinal systems in real situations, i.e., the long-term low-dose exposure, we evaluated and compared the toxicity of three Ag NPs (20-30 nm with different surface coatings) to the human intestine cell Caco-2 after 1-day and 21-day exposures, using various biological assays. In both the short- and long-term exposures, the variety of surface coating predominated the toxicity of Ag NPs in a descending order of citrate-coated Ag NP (Ag-CIT), bare Ag NP (Ag-B), and poly (N-vinyl-2-pyrrolidone)-coated Ag NP (Ag-PVP). The short-term exposure induced cell growth inhibition and death. The cell viability loss appeared after cells were exposed to 0.7 µg/mL Ag-CIT, 0.9 µg/mL Ag-B or >1.0 µg/mL Ag-PVP for 24 h. The short-term and higher-dose exposure also induced reactive oxygen species (ROS) generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation (IL-8 level). The long-term exposure only inhibited the cell proliferation. After 21-day exposure to 0.4 µg/mL Ag-CIT, the cell viability dropped to less than 50%, while cells exposed to 0.5 µg/mL Ag-PVP remained normal as the control. Generally, 0.3 µg/mL is the non-toxic dose for the long-term exposure of Caco-2 cells to Ag NPs in this study. However, cells presented inflammation after exposure to Ag NPs with the non-toxic dose in the long-term exposure.

Biological effect of food additive titanium dioxide nanoparticles on intestine: an in vitro study.

Titanium dioxide nanoparticles (TiO2 NPs) are widely found in food-related consumer products. Understanding the effect of TiO2 NPs on the intestinal barrier and absorption is essential and vital for the safety assessment of orally administrated TiO2 NPs. In this study, the cytotoxicity and translocation of two native TiO2 NPs, and these two TiO2 NPs pretreated with the digestion simulation fluid or bovine serum albumin were investigated in undifferentiated Caco-2 cells, differentiated Caco-2 cells and Caco-2 monolayer. TiO2 NPs with a concentration less than 200 µg ml(-1) did not induce any toxicity in differentiated cells and Caco-2 monolayer after 24 h exposure. However, TiO2 NPs pretreated with digestion simulation fluids at 200 µg ml(-1) inhibited the growth of undifferentiated Caco-2 cells. Undifferentiated Caco-2 cells swallowed native TiO2 NPs easily, but not pretreated NPs, implying the protein coating on NPs impeded the cellular uptake. Compared with undifferentiated cells, differentiated ones possessed much lower uptake ability of these TiO2 NPs. Similarly, the traverse of TiO2 NPs through the Caco-2 monolayer was also negligible. Therefore, we infer the possibility of TiO2 NPs traversing through the intestine of animal or human after oral intake is quite low. This study provides valuable information for the risk assessment of TiO2 NPs in food.