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

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 TiO₂defect structure related to the presence of stoichiometric (Ti⁴⁺) and non-stoichiometric (Ti³⁺and Ti²⁺) titanium ions in the crystal lattice and TiO₂NPs aggregation ability on H₂O₂- and tert-butyl hydroperoxide (tBOOH)-induced ROS production in L929 cells. Synthesized TiO₂-A, TiO₂-B, and TiO₂-C NPs with varying Ti³⁺(Ti²⁺) 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 H₂O₂- and tBOOH-treated L929 cells incubated with TiO₂NPs have been evaluated. Our research shows that both the amount of non-stoichiometric Ti³⁺and Ti²⁺ions in the crystal lattice of TiO₂NPs and NPs aggregative behavior affect their catalytic activity, in particular, H₂O₂decomposition and, consequently, the efficiency of aggravating H₂O₂- and tBOOH-induced oxidative damage to L929 cells. TiO₂-A NPs reveal the strongest H₂O₂decomposition activity aligning with their less pronounced additional effects on H₂O₂-treated L929 cells due to the highest amount of Ti³⁺(Ti²⁺) ions. TiO₂-C NPs with smaller amounts of Ti³⁺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 TiO₂NPs 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.