Short-term and long-term toxicological effects of vanadium dioxide nanoparticles on A549 cells

Abstract

The massive production and wide application of vanadium dioxide nanoparticles (VO₂ NPs) has raised safety concerns of VO₂ NPs exposure through various routes, especially via inhalation. To determine the pulmonary toxicity of VO₂ NPs in vitro, we report here on short-term (1 day) and long-term (20 days) comparative toxicity studies of VO₂ NPs (denoted as C-VO₂, 20–30 nm) and VO₂ microparticles (denoted as M-VO₂, ∼1 μm) on the lung cell line A549. Different toxic effects were observed under different durations of exposures to VO₂ particles. VO₂ particles 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-VO₂ was 2.5 μg ml⁻¹, C-VO₂ causing much more severe cell viability loss than M-VO₂ at the same concentration. For long-term exposure, the cell viability dropped to less than 50% after exposure to C-VO₂ at a dose of 0.2 μg ml⁻¹, while cells exposed to M-VO₂ under the same conditions remained normal, confirming the higher toxicity of C-VO₂ than that of M-VO₂. Moreover, the long-term exposure to C-VO₂ only inhibited the cell proliferation. We found that 0.05 μg ml⁻¹ was the highest non-toxic dose of C-VO₂ to A549 cells for long-term exposure. The dissolution of VO₂ contributed 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 VO₂ particles 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-VO₂ at concentrations of 0.1 μg ml⁻¹ and 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.