Nanoparticle-induced oxidation of corona proteins initiates an oxidative stress response in cells

Titanium dioxide nanoparticles (TiO₂ NPs), used as pigments and photocatalysts, are ubiquitous in our daily lives. Previous work has observed cellular oxidative stress in response to the UV-excitation of photocatalytic TiO₂ NPs. In comparison, most human exposure to TiO₂ NPs takes place in the dark, in the lung following inhalation or in the gut following consumption of TiO₂ NP food pigment. Our spectroscopic characterization shows that both photocatalytic and food grade TiO₂ NPs, in the dark, generate low levels of reactive oxygen species (ROS), specifically hydroxyl radicals and superoxides. These ROS oxidize serum proteins that form a corona of proteins on the NP surface. This protein layer is the interface between the NP and the cell. An oxidized protein corona triggers an oxidative stress response, detected with PCR and western blotting. Surface modification of TiO₂ NPs to increase or decrease surface defects correlates with ROS generation and oxidative stress, suggesting that NP surface defects, likely oxygen vacancies, are the underlying cause of TiO₂ NP-induced oxidative stress.