放射治疗在癌症治疗中起着至关重要的作用。然而，肿瘤的缺氧微环境极大地限制了放疗的有效性，因此开发一种简单、高效、安全的放射增敏剂来逆转缺氧、提高放疗疗效至关重要。受经典纳米药物 Abraxane 结构的启发，本文开发了通过生物矿化诱导的自组装制备的天然 HSA 修饰的 CaO2 纳米颗粒系统（CaO2-HSA）。 CaO2-HSA会在肿瘤组织中积聚并分解产生氧气，改变肿瘤内部的缺氧状况。同时，ROS和钙离子会导致钙超载，进一步引发免疫原性细胞死亡。值得注意的是，其增敏率（SER=3.47）远高于临床使用的缩水双唑钠。此外，在原位口腔癌动物模型中，CaO2-HSA可以有效抑制肿瘤生长。基于 CaO2-HSA 的放射增敏剂具有高效、易于制备和不含重金属的生物安全性，在口腔癌治疗方面具有巨大的潜力。© 2024 作者。 《Advanced Science》由 Wiley‐VCH GmbH 出版。

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 CaO2 nanoparticle system (CaO2-HSA) prepared by biomineralization-induced self-assembly is developed. CaO2-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, CaO2-HSA can effectively inhibit tumor growth. With its high efficacy, facile preparation, and heavy-metal free biosafety, the CaO2-HSA-based radiosensitizer holds enormous potential for oral cancer therapy.© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.