Hydrogel-Assisted Brachytherapy: From Physical Spacing to Functional Synergy.

Brachytherapy (BT) delivers high-dose localized irradiation through the direct implantation of radionuclides into tumor sites and remains an important treatment modality for solid tumors. However, conventional BT is limited by damage to surrounding normal tissues, potential leakage of radionuclides, and the restricted efficacy of single-modality treatment. Hydrogels, owing to their injectability, biocompatibility, and tunable functionality, offer promising solutions to these challenges. This review summarizes recent advances in two principal applications of hydrogel-assisted BT. On the one hand, hydrogels can serve as biodegradable spacers that increase the distance between the target region and organs at risk, thereby reducing radiation exposure to normal tissues such as the rectum and urethra; this approach has demonstrated significant dosimetric advantages and reduced toxicity in prostate and gynecological cancers. On the other hand, hydrogels can function as localized delivery platforms for radionuclides, enabling precise radiotherapy, while also supporting the co-delivery of chemotherapeutic agents, nanoparticles, and immunomodulators to construct dual- or multimodal synergistic treatment strategies. Their potential for enhanced therapeutic efficacy has been demonstrated across various tumor models. Finally, this review critically examines the key technological and clinical translational challenges currently limiting hydrogel-assisted BT and outlines future research directions for more effective and precisely targeted therapies.