Hybrid TiO2–Ruthenium Nano‐photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions

Abstract Photodynamic therapy (PDT) is widely used to treat diverse diseases, but its dependence on oxygen to produce cytotoxic reactive oxygen species (ROS) diminishes the therapeutic effect in a hypoxic environment, such as solid tumors. Herein, we developed a ROS‐producing hybrid nanoparticle‐based photosensitizer capable of maintaining high levels of ROS under both normoxic and hypoxic conditions. Conjugation of a ruthenium complex (N3) to a TiO 2 nanoparticle afforded TiO 2 ‐N3. Upon exposure of TiO 2 ‐N3 to light, the N3 injected electrons into TiO 2 to produce three‐ and four‐fold more hydroxyl radicals and hydrogen peroxide, respectively, than TiO 2 at 160 mmHg. TiO 2 ‐N3 maintained three‐fold higher hydroxyl radicals than TiO 2 under hypoxic conditions via N3‐facilitated electron–hole reduction of adsorbed water molecules. The incorporation of N3 transformed TiO 2 from a dual type I and II PDT agent to a predominantly type I photosensitizer, irrespective of the oxygen content.