Short-term and long-term toxicological effects of vanadium dioxide nanoparticles on A549 cellsElectronic supplementary information (ESI) available. See DOI: 10.1039/c8en00959g

The massive production and wide application of vanadium dioxide nanoparticles (VO2NPs) has raised safety concerns of VO2NPs exposure through various routes, especially viainhalation. To determine the pulmonary toxicity of VO2NPs in vitro, we report here on short-term (1 day) and long-term (20 days) comparative toxicity studies of VO2NPs (denoted as C-VO2, 20–30 nm) and VO2microparticles (denoted as M-VO2, ∼1 μm) on the lung cell line A549. Different toxic effects were observed under different durations of exposures to VO2particles. VO2particles induced cell growth inhibition and death in a dose- and size-dependent style after short-term exposure. The cell viability dropped when the concentration of C-VO2was 2.5 μg ml−1, C-VO2causing much more severe cell viability loss than M-VO2at the same concentration. For long-term exposure, the cell viability dropped to less than 50% after exposure to C-VO2at a dose of 0.2 μg ml−1, while cells exposed to M-VO2under the same conditions remained normal, confirming the higher toxicity of C-VO2than that of M-VO2. Moreover, the long-term exposure to C-VO2only inhibited the cell proliferation. We found that 0.05 μg ml−1was the highest non-toxic dose of C-VO2to A549 cells for long-term exposure. The dissolution of VO2contributed to the cytotoxicity of VO2. In addition, reactive oxygen species (ROS) generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation were observed in the cells after short-term exposure to VO2particles in the concentration range tested, indicating that the possible toxicological mechanism might be ROS generation and cell cycle arrest in the G0/G1 phase. ROS generation, mitochondrial damage, and inflammation in cells were also observed during the long-term exposure to C-VO2at concentrations of 0.1 μg ml−1and 0.2 μg ml−1, but the cells recovered after a subsequent 5 day recovery period. Our results show that there are significant differences between the short-term and long-term cytotoxicities of VO2.