A reactive oxygen species amplifier based on a Bi₂WO₆/BP heterojunction for high efficiency radiotherapy enhancement

Insufficient reactive oxygen species (ROS) generation and radioresistance resulting from the intrinsic features of tumors consistently give rise to unsatisfactory therapeutic outcomes of radiotherapy (RT). Developing a multifunctional radiosensitizer capable of activating ROS-induced apoptosis and achieving multimodal therapy is highly imperative yet remains a challenge so far. Herein, a multifunctional therapeutic nanoplatform based on Bi₂WO₆-BP heterojunctions for multimodal synergistic tumor treatment with glutathione depletion and amplifying ROS generation is rationally designed. Rich in high-Z elements, Bi₂WO₆-BP heterojunctions are able to deposit higher radiation doses into cancer cells, enhancing the radiotherapy effect. The Z-scheme heterojunction structure facilitates the X-ray-triggered catalytic process that catalyzes intracellular overproduced H₂O₂ into highly toxic ˙OH, which thus enhances ROS generation in a hypoxic environment. The unique sub-band structures of BP NSs and the synergistic effect between Bi₂WO₆ and BP significantly boosted ¹O₂ generation. Meanwhile, the acidic TME can trigger the cycle conversion of W from W⁵⁺ to W⁶⁺, and the redox reaction between W⁶⁺ and GSH consumes the high level of GSH in tumor cells and increases the production of ROS. The mild photothermal effect produced by the Bi₂WO₆-BP heterojunction could further enhance the ROS generation. Both in vitro and in vivo experiments showed that the as-prepared Bi₂WO₆-BP heterojunction possesses high synergistic therapeutic efficacy. This work offers a viable approach to build a multifunctional radiosensitizer with TME-triggered multiple synergistic therapies for deep tumors.