Multifunctional Cu3BiS3-BP@PEI Radiosensitizer with Enhanced Reactive Oxygen Species Activity for Multimodal Synergistic Therapy

Development of radiosensitizers with high-energy deposition efficiency, electron transfer, and oxidative stress amplification will help to improve the efficiency of radiotherapy. To overcome the drawbacks of radiotherapy alone, it is also crucial to design a multifunctional radiosensitizer that simultaneously realizes multimodal treatment and tumor microenvironment modulation. Herein, a multifunctional radiosensitizer based on the Cu3BiS3-BP@PEI nanoheterostructure (NHS) for multimodal cancer treatment is designed. Cu3BiS3-BP@PEI NHS is able to deposit a high radiation dose into cancer cells, enhancing the radiotherapy effect. Due to the heterostructure and the synergistic effect of Cu3BiS3 and black phosphorus (BP), significantly boosted 1O2 and •OH generation is obtained under X-ray irradiation, which is promising for extremely efficient radiodynamic therapy. More importantly, the acidic tumor microenvironment (TME) can induce the cycle conversion of Cu2+ to Cu+, oxidizing glutathione (GSH) and catalyzing intracellular overproduction of H2O2 into highly toxic •OH, which thus further enhances reactive oxygen species (ROS) production and reduces GSH-associated radioresistance. Furthermore, Cu3BiS3-BP@PEI NHS has an excellent photothermal effect and can effectively transform light into heat. The outcomes of the in vitro and in vivo research confirm that the as-prepared Cu3BiS3-BP@PEI NHS has a high synergistic therapeutic efficacy at a low radiation dose. This work provides a viable approach to constructing a multifunctional radiosensitizer for deep tumor treatment with TME-triggered multiple synergistic therapies.