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

Abstract

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