Construction of a nanozyme composite drug delivery system based on columbianadin for inflammatory bowel disease therapy.

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 (O2) 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.