A Radio‐Pharmaceutical Fluorescent Probe for Synergistic Cancer Radiotherapy and Ratiometric Imaging of Tumor Reactive Oxygen Species

Abstract Radiotherapy (RT) is an effective and widely applied cancer treatment strategy in clinic. However, it usually suffers from radioresistance of tumor cells and severs side effects of excessive radiation dose. Therefore, it is highly significant to improve radiotherapeutic performance and monitor real‐time tumor response, achieving precise and safe RT. Herein, an X‐ray responsive radio‐pharmaceutical molecule containing chemical radiosensitizers of diselenide and nitroimidazole (BBT‐IR/Se‐MN) is reported. BBT‐IR/Se‐MN exhibits enhanced radiotherapeutic effect via a multifaceted mechanisms and self‐monitoring ROS levels in tumors during RT. Under X‐ray irradiation, the diselenide produces high levels of ROS, leading to enhanced DNA damage of cancer cell. Afterwards, the nitroimidazole in the molecule inhibits the damaged DNA repair, offering a synergetic radiosensitization effect of cancer. Moreover, the probe shows low and high NIR‐II fluorescence ratios in the absence and presence of ROS, which is suitable for precise and quantitative monitoring of ROS during sensitized RT. The integrated system is successfully applied for radiosensitization and the early prediction of in vitro and in vivo RT efficacy.