Bioactive hydrogels in radiation sensitization and protection: New strategies and challenges

Radiotherapy is one of the core modalities for clinical tumor treatment. However, numerous limitations and side effects of radiotherapy, such as the inherent radioresistance of tumor cells and radiation-induced damage to normal tissues, have seriously affected the therapeutic efficacy and quality of life of cancer patients. Therefore, the precise drug delivery strategies for radiotherapy sensitization and radiation protection have become a critical direction for optimizing radiotherapy regimens. To address this challenge, the bioactive hydrogels with the dual functions of "enhancing radiotherapy efficacy" and "alleviating radioactive damage" have emerged. Endowed with excellent biocompatibility, local targeting ability, and customizable functionality, these hydrogels have demonstrated promising "efficacy enhancement and toxicity reduction" effects in preclinical studies. In-depth analysis of the design principles, mechanisms of action, and application characteristics of radiotherapy-sensitizing and radiation-protective hydrogels holds significant guiding significance for the innovative development and clinical translation of subsequent functional hydrogels. This article comprehensively reviews the recent advances in the design and application of hydrogels in drug delivery for radiotherapy sensitization and radiation protection. On one hand, the core strategies of radiotherapy sensitization, sensitizing components, as well as the design and application of radiotherapy-sensitizing hydrogels are widely summarized and discussed. On the other hand, the strategies for radiation protection and the application of radiation-protective hydrogels in the treatment of various radiation-induced injuries are outlined in detail. Finally, the future development directions of the bioactive hydrogels with "efficacy enhancement and toxicity reduction" properties are further proposed.