Abstract
Inflammatory bowel disease (IBD) is characterized by chronic gastrointestinal inflammation driven by oxidative stress and immune dysregulation. This study develops a novel oral nanozyme composite drug delivery system (MXene/CBN@GelMA, MCG) designed for targeted therapy of IBD. The composite integrates antioxidative MXene nanosheets and anti-inflammatory columbianadin (CBN) into a gelatin methacryloyl (GelMA) hydrogel, enabling targeted delivery and therapy. MCG efficiently scavenges reactive oxygen species (ROS) and generates oxygen (O(2)) through a superoxide dismutase (SOD)-catalase (CAT) cascade reaction, thereby alleviating oxidative stress and mitigating hypoxia in the inflamed tissues. In a dextran sulfate sodium (DSS)-induced IBD model, MCG treatment significantly reduced disease activity, restored colon length, preserved mucosal integrity, and suppressed pro-inflammatory pathways. Transcriptomic analysis revealed that MCG reversed IBD-associated gene expression dysregulation and modulated immune-related pathways. The system demonstrated high biocompatibility and effective targeting, providing a synergistic therapeutic strategy for IBD through antioxidative and anti-inflammatory mechanisms.