Cytotoxicity and RNA-sequencing analysis of macrophages after exposure to vanadium dioxide nanoparticles

Abstract

Extensive applications of vanadium dioxide (VO₂)-based materials raise concerns over the biosafety of VO₂ exposure via various routes. To understand the effects of VO₂ on people's health, we used RNA sequencing (RNA-seq) to monitor the widespread changes in gene expression to reveal the toxicity mechanism of two commercial VO₂ materials, nanoscale VO₂ (S-VO₂) and bulk VO₂ (M-VO₂), on the RAW264.7 cell line, which represents the first cellular systems dealing with xenobiotics. Nanoscale S-VO₂ displayed higher toxicity than bulk M-VO₂, but both VO₂ particles inhibited the proliferation and induced apoptosis in RAW264.7 cells with similar toxicity mechanisms. As shown by RNA-seq analysis and validated by biochemical assays, VO₂ particles induced endoplasmic reticulum stress accompanied by the release of calcium ions and the overproduction of reactive oxygen species, leading to DNA damage, mitochondrial damage, autophagy and lysosomal damage, which finally resulted in apoptosis and proliferation inhibition, showing a decline in viability. The cellular uptake of VO₂ particles and the dissolved species of VO₂ jointly contributed to the observed toxicity. This systematic study reveals the toxicity mechanisms of VO₂ materials at the transcriptome level, providing valuable data for their safe applications in the future.