Silica nanoparticles induce mitochondrial pathway‐dependent apoptosis by activating unfolded protein response in human neuroblastoma cells

Abstract The application of silica nanoparticles (SiNPs) in areas of agriculture and medicine has raised great concerns for the potential adverse effects of SiNPs. The increasing toxicological studies focused mainly on the lung and cardiovascular system, but the adverse effects of SiNPs on nervous system have not been well explored. This study aimed to evaluate the role and mechanism of unfolded protein reaction (UPR) in SiNPs‐induced cell injury on nerve cells in vitro. We investigated the UPR‐mediated apoptosis caused by SiNPs in human neuroblastoma (SH‐SY5Y) cell line. The size of SiNPs and its effect on cell ultrastructure were observed by transmission electron microscopy (TEM). Cell growth, mitochondrial membrane potential (MMP), calcium ion (Ca 2+ ), apoptosis rate, and the expression level of related proteins were evaluated using MTT, flow cytometry, and western blot in SH‐SY5Y cells exposed to SiNPs. The results showed that with the increase of SiNPs concentration, cell viability decreased, MMP decreased, active oxygen (ROS), and Ca 2+ levels increased in a dose‐dependent manner. In addition, protein expression of PERK, GRP78, and other related proteins in the unfolded protein response increased in a dose‐response manner together with the expression of apoptosis proteins. Conclusively, this study confirmed that SiNPs can affect the neural system by interfering structure and functional and inducing apoptosis in nerve cells through unfolded protein response.