Engineered dual-responsive mucoadhesive hydrogel co-delivering fullerenol against radiation-induced vaginal injury and microbiota dysbiosis.

Radiation-induced vaginal injury (RIVI) is a prevalent complication following pelvic radiotherapy for gynecological cancers, which is mainly caused by severe mucosal oxidative stress triggered by highly destructive reactive oxygen species (ROS), such as hydroxyl radicals (·OH). Conventional prophylactic agents struggle due to instability, inadequate radical targeting, and short residence time in the vaginal lumen. To overcome the existing challenges, we develop a biomaterial-based prophylactic strategy that enables effective neutralization of toxic radicals and smart mucosal adhesion. Taking advantage of carbon-based nano-antioxidant fullerenol (FOH) as a reliable "radical sponge" for ·OH clearance, we engineer pH- and temperature-responsive amino-terminated Pluronic F127 (AF127) in situ hydrogel as the carrier of FOH. The AF127@FOH system is suitable for facile vaginal administration and can achieve in situ gelation. More importantly, AF127 can be protonated in the acidic vaginal environment, thereby enhancing mucoadhesion with vaginal mucins through electrostatic interactions and prolonging local residence. This design enables a locally sustained release of FOH, which inhibits the initial burst of ROS, mitigating oxidative damage, early tissue damage, and subsequent vaginal microbial dysbiosis. Our work provides an advanced topical treatment approach for RIVI and expands the application of smart biomaterials in mucosal radiation protection.