Oral ROS-responsive hydrogel with sulfur-doped ginger carbon dots for modulating oxidative stress and restoring gut homeostasis in inflammatory bowel disease

Carbon dots with dual enzyme-like activities of SOD and CAT-like were synthesized. • An orally administered precursor solution underwent ROS-responsive gelation at sites of colonic inflammation. • Inverting M1/M2 macrophage imbalance and recruiting Treg cells to drive immune responses. • Restoring intestinal integrity and rebalancing the gut microbiota. Inflammatory bowel disease (IBD) involves a complex inflammatory environment marked by excessive oxidative stress, impaired barrier function, and microbial imbalance. These interconnected pathologies are difficult to address with conventional single-target therapies. To tackle these challenges, this study developed an intelligently responsive oral hydrogel delivery system based on sulfur-doped ginger carbon dots (SGCDs). SGCDs, synthesized via a hydrothermal method, not only exhibited remarkable antioxidant capacity but also demonstrated multiple enzyme-like activities, including SOD-like and CAT-like, along with stable fluorescence imaging properties. Simultaneously, thiolated hyaluronic acid (HS 1:6 ), exhibiting ROS-responsive gelation properties, was synthesized via chemical modification and employed as the gel matrix. The oral precursor system (HS 1:6 @SGCDs), constructed by loading SGCDs into the HS solution, underwent ROS-triggered in situ gelation upon reaching the colonic inflammatory region. This transformation formed a physical barrier, prolonged retention time, and enabled controlled release of SGCDs. This system significantly alleviated pathological symptoms through multiple mechanisms, including efficient scavenging of excessive ROS, modulation of the immune microenvironment, amelioration of intestinal barrier dysfunction, and amelioration of dysbiosis with a trend toward recovery of a more balanced microbial community. Through disease-directed and source-based innovation, the system combined targeted material design with multifunctional therapeutic capabilities. Thus, HS 1:6 @SGCDs provided an innovative and comprehensive solution for the treatment of IBD.