Combined effects of different sizes of ZnO and ZIF-8 nanoparticles co-exposure with Cd2+ on HepG2 cells

Highlights: • The combined effect of zinc-based NPs with Cd²⁺ depends on the concentration of NPs. • High-dose of zinc-based NPs or Zn²⁺ co-exposure with Cd²⁺ would decrease the cell viability. • Particle sizes of zinc-based NPs have no obvious effect on the combined toxicity. • Low-dose of zinc-based NPs or Zn²⁺ co-exposure with Cd²⁺ has different detoxification mechanisms for cells. • Decreasing the cellular Cd amount is the main way of detoxification for zinc-based NPs in the antagonism. Heavy metal and nanoparticles (NPs) emitted in the environment have attracted worldwide attention. But the combined effect of NPs and heavy metals is still unclear. In this study, the combined effect of zinc-based NPs and Cd²⁺ on HepG2 cells was investigated by combining biological indicator detection methods with time-resolved inductively coupled plasma mass spectrometry (TRA-ICP-MS) single cell analysis, and the combined effect of Zn²⁺ and Cd²⁺ was also investigated for a comparison. High-dose of ZnO or ZIF-8 NPs co-exposure with Cd²⁺ would reduce the cell viability while low-dose of ZnO or ZIF-8 NPs co-exposure with Cd²⁺showed antagonism and the particle size has no remarkable effect on the combined toxicity. In the antagonism, Zn²⁺ would increase cellular Zn amount through increasing the expression of ZIP8 and ZIP14 transporters to manage the ROS generation, but the zinc-based NPs would decrease expression of these transporters to decrease cellular Cd amount to help maintain the cell viability. Thus, we should hold a dialectical thinking about the pollution of NPs emissions in the environment.