Stimuli-Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

Radiotherapy (RT) has been a classical therapeutic method of cancer for several decades. It attracts tremendous attention for the precise and efficient treatment of local tumors with stimuli-responsive nanomaterials, which enhance RT. However, there are few systematic reviews summarizing the newly emerging stimuli-responsive mechanisms and strategies used for tumor radio-sensitization. Hence, this review provides a comprehensive overview of recently reported studies on stimuli-responsive nanomaterials for radio-sensitization. It includes four different approaches for sensitized RT, namely endogenous response, exogenous response, dual stimuli-response, and multi stimuli-response. Endogenous response involves various stimuli such as pH, hypoxia, GSH, and reactive oxygen species (ROS), and enzymes. On the other hand, exogenous response encompasses X-ray, light, and ultrasound. Dual stimuli-response combines pH/enzyme, pH/ultrasound, and ROS/light. Lastly, multi stimuli-response involves the combination of pH/ROS/GSH and X-ray/ROS/GSH. By elaborating on these responsive mechanisms and applying them to clinical RT diagnosis and treatment, these methods can enhance radiosensitive efficiency and minimize damage to surrounding normal tissues. Finally, this review discusses the additional challenges and perspectives related to stimuli-responsive nanomaterials for tumor radio-sensitization. This review systematically concludes the strategies of stimuli-responsive nanomaterials for sensitized RT, elaborates on the radiosensitization mechanism and responsive process of stimuli-responsive nanoradiosensitizers in detail, highlights potential challenges and promises of stimuli-responsive radiosensitizers, and provides a pathway for their further development and use in clinical practice.image