Abstract

Inflammatory bowel disease (IBD) represents a chronic inflammatory disorder characterized by excessive reactive oxygen species (ROS) generation, persistent inflammatory response, and gut microbiota dysbiosis. Herein, a novel colon-targeted composite hydrogel (FTS/Gel) consisting of metal-polyphenol nanozymes (FTS) embedded in an inulin-based gel was developed for efficient oral treatment of IBD. This nanozyme (FTS) was synthesized by coordination between Fe 3+ ions and the anti-inflammatory drugs taxifolin (Tax) and L- Se -methylselenocysteine (SeMC), exhibiting remarkable superoxide dismutase (SOD)-like and catalase (CAT)-like activities. Moreover, FTS nanozymes significantly scavenged intracellular ROS and suppressed inflammation in RAW264.7 cells. Incorporating FTS into an inulin hydrogel notably enhanced colon-targeting efficiency, bio-adhesion, and retention time in vivo. Oral administration of FTS/Gel effectively alleviated colitis, as evidenced by increased colon length, reduced splenomegaly, restored intestinal epithelial barrier integrity, and enhanced mucin secretion. Furthermore, FTS/Gel treatment rebalanced gut microbiota composition by promoting beneficial bacteria and suppressing pernicious bacteria. Collectively, this study presents a promising therapeutic strategy combining antioxidant nanozymes and prebiotic-based hydrogel delivery systems for effectively managing and treating IBD.