Light-Responsive Ru–Se Coordinated Nanoreactor Spatiotemporally Relieves Hypoxia for Photodynamic Therapy of Bladder Cancer

Photodynamic therapy (PDT) has been employed as a noninvasive treatment option for bladder cancer due to its controllability and minimal toxicity. However, the efficacy of PDT is often compromised by the hypoxic microenvironment of solid tumors. To address this challenge, our research is dedicated to developing a Ru-Se-Ce6 nanoreactor that combines the photoresponsiveness of Ru-Se coordination bonds and the reactive oxygen species (ROS) triggered by diselenide bonds, achieving dual-controlled release of the photosensitizer to enhance PDT effectiveness. The photoresponsive and catalytic characteristics of the nanoreactor were validated through synchrotron radiation and density functional theory calculations. Under laser irradiation, a metal-to-ligand charge transfer (MLCT) within the ruthenium complex leads to the cleavage of the Ru-Se bond, resulting in the liberation of the ruthenium complex, which significantly improves the O2 generation from H2O2 in the tumor microenvironment (TME). In vivo assessments demonstrated that Ru-Se-Ce6 disrupted the mitochondrial membrane potential via excessive ROS production, leading to cell cycle arrest and apoptosis. Additionally, Ru-Se-Ce6 has revealed significant tumor suppression in subcutaneous and orthotopic bladder tumor models while exhibiting good biocompatibility. These findings propose a potent and innovative approach for bladder cancer therapy.