X-ray-Responsive Cascade System with Pt/SnO2–x Heterojunction as Initiators: Fabrication and Investigation for Radiosensitization

Triple-negative breast cancer (TNBC) exhibits strong radiotherapy resistance. A cascade system of Pt/SnO2–x@PDA@CaP-GOx initiated by X-rays was innovatively proposed first to enhance the radiotherapy sensitivity in terms of hypoxia-related radiotherapy resistance. By using the X-ray-responsive cascade system, not only the penetration depth could be ignored but also the advantages of radiotherapy could be effectively utilized. Through alleviating hypoxia and boosting reactive oxygen species (ROS) generation, excellent radiosensitivity could be achieved by the X-ray-responsive cascade enzymatic reaction system. Including H2O2 formation, O2 production, and ROS release, a series of explorations confirmed the formation of a complete X-ray-responsive cascade system. In vitro studies on 4T1 cells demonstrated that 81% killing rate could be achieved by the cascade system through DNA damage and HIF-1α regulation to alleviate hypoxia. The tumor proliferation was effectively inhibited, and its volume has reduced to 3% of the original solid tumor in the in situ transplantation tumor model. This work presents Pt/SnO2–x@PDA@CaP-GOx as a highly effective X-ray-responsive radiosensitizer, offering a promising strategy for TNBC radiotherapy.