Oxidative stress-modifying effects of TiO2 nanoparticles with varying content of Ti3+(Ti2+) ions

Abstract Nanoparticles (NPs) with reactive oxygen species (ROS)-regulating ability have recently attracted great attention as promising agents for nanomedicine. In the present study, we have analyzed the effects of TiO 2 defect structure related to the presence of stoichiometric (Ti 4+ ) and non-stoichiometric (Ti 3+ and Ti 2+ ) titanium ions in the crystal lattice and TiO 2 NPs aggregation ability on H 2 O 2 - and tert-butyl hydroperoxide (tBOOH)-induced ROS production in L929 cells. Synthesized TiO 2 -A, TiO 2 -B, and TiO 2 -C NPs with varying Ti 3+ (Ti 2+ ) content were characterized by x-ray powder diffraction, transmission electron microscopy, small-angle x-ray scattering, x-ray photoelectron spectroscopy, and optical spectroscopy methods. Given the role of ROS-mediated toxicity for metal oxide NPs, L929 cell viability and changes in the intracellular ROS levels in H 2 O 2 - and tBOOH-treated L929 cells incubated with TiO 2 NPs have been evaluated. Our research shows that both the amount of non-stoichiometric Ti 3+ and Ti 2+ ions in the crystal lattice of TiO 2 NPs and NPs aggregative behavior affect their catalytic activity, in particular, H 2 O 2 decomposition and, consequently, the efficiency of aggravating H 2 O 2 - and tBOOH-induced oxidative damage to L929 cells. TiO 2 -A NPs reveal the strongest H 2 O 2 decomposition activity aligning with their less pronounced additional effects on H 2 O 2 -treated L929 cells due to the highest amount of Ti 3+ (Ti 2+ ) ions. TiO 2 -C NPs with smaller amounts of Ti 3+ ions and a tendency to aggregate in water solutions show lower antioxidant activity and, consequently, some elevation of the level of ROS in H2O2/tBOOH-treated L929 cells. Our findings suggest that synthesized TiO 2 NPs capable of enhancing ROS generation at concentrations non-toxic for normal cells, which should be further investigated to assess their possible application in nanomedicine as ROS-regulating pharmaceutical agents.