ABSTRACT Radiotherapy (RT) is one of the cornerstones in cancer treatment, with approximately 50% of patients receiving radiation regimens annually. However, its clinical efficacy is constrained by two persistent challenges: tumor radioresistance and radiation‐induced damage to healthy tissues. Recent advances in nanomedicine have yielded innovative nano‐radiosensitizers capable of enhancing tumor‐specific radiation dose deposition while sparing normal tissues, thereby addressing both limitations simultaneously. Previous advanced reviews have extensively covered intrinsic nanomaterial properties and physicochemical mechanisms of radiosensitization; this review systematically elucidates radiosensitization mechanisms through the lens of RT subprocesses, offering a novel framework to evaluate how specific mechanisms modulate discrete stages of radiation response. It includes increasing radiation dose deposition; lowering antioxidant system level to promote ROS production; collaborating with other ways to promote ROS production; collaborating with the production of exogenous cytotoxic substances; augmenting intrinsic radiosensitivity of cancer cells; stabilizing radiation‐induced DNA lesions to suppress repair machinery; and enhancing radiogenic immunogenic cell death to strengthen antitumor immunity. Furthermore, we discuss emerging trends in nanotechnology‐driven combination therapies. This systematic perspective advances the rational design of next‐generation nano‐radiosensitizers and informs personalized radiotherapy protocols. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Zhou et al. (Mon,) studied this question.