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.