An orally deliverable Co₃O₄@MMT nanozyme platform for inflammatory bowel disease via ROS scavenging, barrier repair,...

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by a self-perpetuating pathological loop, where excessive reactive oxygen species (ROS) induce mucosal inflammation, which in turn drives further ROS production. This oxidative-inflammatory cycle leads to intestinal epithelial barrier disruption and gut microbiota dysbiosis. Current immunosuppressive therapies primarily target downstream inflammation, while fail to address the foundational oxidative stress and achieve complete mucosal healing. To bridge this gap, we developed an orally deliverable nanozyme platform by anchoring cobalt oxide (Co₃O₄) nanoparticles onto montmorillonite nanosheets (Co₃O₄@MMT). This design leverages the Co²⁺/Co³⁺ redox cycling within Co₃O₄ for efficient multi-enzymatic ROS scavenging. Furthermore, transcriptomic analysis and literature evidence suggest that the released Co²⁺ ions can activate the HIF-1α pathway-a key regulator of epithelial repair. The MMT component protects the nanozyme from gastrointestinal degradation and facilitates its electrostatic accumulation at inflamed colonic sites. In murine colitis models, oral Co₃O₄@MMT treatment effectively alleviated disease severity, suppressed inflammation, restored barrier integrity, and rebalanced gut microbiota. This work presents an integrated oral strategy that concurrently targets oxidative stress, inflammation, and barrier restoration, offering a comprehensive therapeutic approach for IBD.