Hydrogel-Based Approaches for Radiation Protection in Radiotherapy

As one of the primary modalities for cancer treatment, radiotherapy (RT) utilizes high-energy radiation to eradicate cancer cells or inhibit tumor growth and is widely employed in clinical practice. However, while targeting malignant cells, radiation can also cause unintended damage to surrounding healthy tissues, leading to serious complications that adversely affect patient prognosis and quality of life. In recent years, hydrogels have emerged as promising adjuvant systems for RT due to their tunable physicochemical properties, excellent biocompatibility, and capacity for multifunctional integration. This review systematically summarizes recent advances in hydrogel-based platforms designed for radiation protection and therapy enhancement, focusing on how material composition and morphological design enable localized modulation of radiation dose, proactive prevention of side effects, and coordinated intervention in the tumor microenvironment. The review aims to provide a comprehensive resource for understanding the multifunctional roles of hydrogels in RT and to explore their potential pathways toward clinical translation, with the goal of advancing precise, low-toxicity, and personalized radiotherapy. • Hydrogels enable localized, sustained delivery of radioprotective agents and radiosensitizers, overcoming limitations of systemic administration. • Thermo-responsive hydrogels offer injectable formulations that undergo sol-gel transition at body temperature, facilitating minimally invasive application. • As physical spacers, hydrogels significantly reduce radiation doses to organs-at-risk. • Multifunctional platforms integrating imaging contrast, radiosensitization, and therapeutic delivery represent the future direction for personalized, precision radiotherapy.