Hydrogel-enhanced brachytherapy in cervical cancer: redefining precision, efficacy, and safety

Cervical cancer remains a major global health challenge, with over 600,000 new cases and 340,000 deaths annually, predominantly in low- and middle-income countries, where gaps in screening and access to advanced therapies sustain high morbidity and mortality. Standard treatment for locally advanced disease relies on radiotherapy-particularly brachytherapy-which delivers highly conformal, high-dose radiation directly to tumors. However, conventional brachytherapy is limited by a narrow therapeutic window: the proximity of radiosensitive organs, tumor hypoxia, immunosuppressive stroma, and anatomical variability restrict dose escalation and compromise tumor control. Hydrogel-based biomaterials have emerged as a transformative solution. Serving simultaneously as organ-protective spacers, localized radiosensitizers, and multifunctional drug delivery platforms, hydrogels enable precision-guided modulation of the tumor microenvironment while protecting adjacent tissues. Advanced designs-including injectable, implantable, stimulus-responsive, and 3D-printable hydrogels-allow patient-specific, tumor-targeted interventions that synergize brachytherapy with chemotherapy, immunotherapy, or nanoparticle-based radiosensitizers. Preclinical and early clinical studies demonstrate improved tumor response, reduced radiation-induced toxicity, and expanded therapeutic windows. This review synthesizes the mechanistic rationale, preclinical evidence, and clinical experience of hydrogel-assisted brachytherapy. By bridging materials science and oncology, hydrogel platforms represent a paradigm shift-safely expanding the therapeutic window, enhancing tumor eradication, and minimizing toxicity in cervical cancer.