Cytotoxicity of vanadium dioxide nanoparticles to human embryonic kidney cell line: Compared with vanadium(IV/V) ions

Vanadium dioxide (VO₂) is a class of thermochromic material with potential applications in various fields. Massive production and wide application of VO₂ raise the concern of its potential toxicity to human, which has not been fully understood. Herein, a commercial VO₂ nanomaterial (S-VO₂) was studied for its potential toxicity to human embryonic kidney cell line HEK293, and two most common vanadium ions, V(IV) and V(V), were used for comparison to reveal the related mechanism. Our results indicate that S-VO₂ induces dose-dependent cellular viability loss mainly through the dissolved V ions of S-VO₂ outside the cell rather than S-VO₂ particles inside the cell. The dissolved V ions of S-VO₂ overproduce reactive oxygen species to trigger apoptosis and proliferation inhibition via several signaling pathways of cell physiology, such as MAPK and PI3K-Akt, among others. All bioassays indicate that the differences in toxicity between S-VO₂, V(IV), and V(V) in HEK293 cells are very small, supporting that the toxicity is mainly due to the dissolved V ions, in the form of V(V) and/or V(IV), but the V(V)'s behavior is more similar to S-VO₂ according to the gene expression analysis. This study reveals the toxicity mechanism of nanosized VO₂ at the molecular level and the role of dissolution of VO₂, providing valuable information for safe applications of vanadium oxides.