“Abraxane‐Like” Radiosensitizer for In Situ Oral Cancer Therapy

Abstract Radiotherapy plays a vital role in cancer therapy. However, the hypoxic microenvironment of tumors greatly limits the effectiveness, thus it is crucial to develop a simple, efficient, and safe radiosensitizer to reverse hypoxia and ameliorate the efficacy of radiotherapy. Inspired by the structure of canonical nanodrug Abraxane, herein, a native HSA‐modified CaO 2 nanoparticle system (CaO 2 ‐HSA) prepared by biomineralization‐induced self‐assembly is developed. CaO 2 ‐HSA will accumulate in tumor tissue and decompose to produce oxygen, altering the hypoxic condition inside the tumor. Simultaneously, ROS and calcium ions will lead to calcium overload and further trigger immunogenic cell death. Notably, its sensitizing enhancement ratio (SER = 3.47) is much higher than that of sodium glycididazole used in the clinic. Furthermore, in animal models of in situ oral cancer, CaO 2 ‐HSA can effectively inhibit tumor growth. With its high efficacy, facile preparation, and heavy‐metal free biosafety, the CaO 2 ‐HSA‐based radiosensitizer holds enormous potential for oral cancer therapy.