Size-dependent cytotoxicity study of ZnO nanoparticles in HepG2 cells

Zinc oxide (ZnO) nanoparticles (NPs) are widely used in daily life. However, common utilization of ZnO NPs results in increases in environmental release, and their health hazards have attracted extensive attention. To investigate the cytotoxicity of ZnO NPs and their mechanism in HepG2 cells, a comprehensive analytical system was developed. The internalization, cytotoxic mechanism, death mechanism and elimination behavior of three sizes of ZnO NPs were studied by electrothermal vaporization (ETV)-inductively coupled plasma mass spectrometry (ICP-MS), MIT assays, GSH measurements, ROS measurements and analyses of apoptosis and gene expression. The size-, dose- and time-dependent characteristics of ZnO NPs were determined, and the metabolism of ZnO NPs in cells was discussed. The cytotoxicity of ZnO NPs was confirmed to depend on both the size and concentration and was attributed to the release of Zn2+, induction of oxidative stress and inflammatory response; the death mode of HepG2 cells incubated with ZnO NPs was necrotic rather than programmed cell death.