Recent Progress in Radiosensitive Nanomaterials for Radiotherapy-Triggered Drug Release

Benefiting from the unique properties of ionizing radiation, such as high tissue penetration, spatiotemporal resolution, and clinical relevance compared with other external stimuli, radiotherapy-induced drug release strategies are showing great promise in developing effective and personalized cancer treatments. However, the requirement of high doses of X-ray irradiation to break chemical bonds for drug release limits the application of radiotherapy-induced prodrug activation in clinics. Recent advances in nanomaterials offer a promising approach for radiotherapy sensitization as well as integrating multiple modalities for improved therapy outcomes. In particular, the catalytic radiosensitization that utilizes electrons and energy generated by nanomaterials upon X-ray irradiation has demonstrated excellent potential for enhanced radiotherapy. In this Review, we summarize the design principles of X-ray-responsive chemical bonds for controlled drug release, strategies for catalytic radiosensitization, and recent progress of X-ray-responsive nanoradiosensitizers for enhanced radiotherapy by integration with chemotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, gas therapy, and immunotherapy. Finally, we discuss the challenges of X-ray-responsive nanoradiosensitizers heading toward possible clinical translation. We expect that emerging strategies based on radiotherapy-triggered drug release will facilitate a frontier in accurate and effective cancer therapy in the near future.