Multifunctional Oral Hydrogel Containing Dual-Active Pt/Mn3O4 Nanozyme for Synergistic Pyroptosis Suppression and Gut Microenvironment Reprogramming to Alleviate Radiation Intestinal Injury.

Radiation intestinal injury (RII) is a severe complication of abdominal and pelvic radiotherapy, driven by excessive reactive oxygen species (ROS), pyroptotic cell death, and gut microbiota dysbiosis. Conventional antioxidants are insufficient, as radical scavenging alone cannot suppress pyroptosis or restore immune-microbiota balance. Herein, we developed a Pt/Mn3O4 nanozyme-curcumin co-loaded multifunctional oral hydrogel (PMC@Gel), which integrates dual-active catalysis and autophagy induction for comprehensive intervention. The heterostructured Pt/Mn3O4 nanozyme exhibits a core-satellite architecture with Pt-O-Mn interfacial bonds, enabling accelerated Mn redox cycling and complementary catalase- and SOD-like activities for broad-spectrum ROS elimination. These components were co-encapsulated in a pH-responsive sodium alginate/sodium hyaluronate hydrogel, providing controlled intestinal release, strong mucosal adhesion, and prolonged retention. In vivo, PMC@Gel efficiently suppressed pyroptosis via ROS clearance, restored autophagy through curcumin, and reprogrammed the gut immune-microbiota microenvironment, thereby alleviating inflammation and promoting epithelial repair. This work introduces a mechanistically integrated hydrogel that synergizes pyroptosis suppression with gut microenvironment reprogramming, offering a promising strategy for RII therapy and a paradigm for autophagy activation, gut microenvironment, nanozyme, pyroptosis, radiation intestinal injurymultifunctional nanozyme-based materials in complex disease treatment.