Engineering Charge Separation in a Bi2MoO6/Black Phosphorus Heterostructured Nanoplatform to Boost Glutathione Depletion for Photothermal-Amplified Radio-Radiodynamic Therapy

Abstract Radiotherapy-radiodynamic therapy (RT-RDT) represents an advanced approach to overcome tumor radioresistance. However, its therapeutic outcome is heavily compromised by the tumor microenvironment (TME), particularly the overexpression of glutathione (GSH, up to 10 mM). Herein, a heterostructured nanoplatform composed of Bi2MoO6 and black phosphorus (denoted as BMO-BP) is developed for multimodal TME remodeling to achieve photothermal-amplified radio-radiodynamic therapy. The heterojunction formed between BMO and BP facilitates efficient charge carrier separation and suppresses electron−hole recombination, significantly boosting X-ray-triggered reactive oxygen species (ROS) production. Electron transfer at the BMO-BP interface promotes the cyclic valence transition of Mo5+/Mo6+, establishing a self-sustaining GSH depletion-ROS generation system for chemodynamic therapy (CDT). Moreover, the BMO-BP nanoplatform exhibits a pronounced photothermal effect upon 808 nm NIR irradiation, which sensitizes DNA to radiation- and ROS-induced damage. In vitro and in vivo experiments demonstrate that the BMO-BP nanoplatform effectively remodels the TME and achieves potent tumor suppression (84% inhibition) through the seamless integration of CDT-mediated GSH depletion and PTT-assisted radiosensitization into the RT-RDT regimen. This study introduces a multifunctional nanoplatform that offers a promising strategy to circumvent microenvironment-mediated radioresistance via photothermal-amplified RT-RDT.