Hypoxic Tumor Radiosensitization Using Engineered Probiotics

Abstract Owing to their ability to rapidly proliferate in specific niches and their amenability to genetic manipulation, bacteria are frequently studied as potential diagnostic or therapeutic bioagents in a range of pathological contexts. A sustained oxygen supply within solid tumors is essential in order to achieve positive radiotherapy (RT) outcomes, as these intratumoral oxygen levels are necessary to facilitate RT‐induced reactive oxygen species (ROS) generation. In this study, a genetically engineered variant of the tumor‐targeting probiotic E. coli Nissle 1917 bacteria that secret catalase is utilized to alleviate intratumoral hypoxia and to thereby enhance tumor radiosensitivity. These engineered bacteria are able to facilitate robust O 2 evolution and consequent ROS generation in response to X‐ray irradiation both in vitro and in vivo, significantly inhibiting tumor growth. Overall, the study highlights a novel and practical approach to enhance the efficacy of tumor RT, underscoring the value of future research in the field of probiotic medicine.