An orally deliverable Co3O4@MMT nanozyme platform for inflammatory bowel disease via ROS scavenging, barrier repair, and mucosal homeostasis regulation

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 (Co 3 O 4 ) nanoparticles onto montmorillonite nanosheets (Co 3 O 4 @MMT). This design leverages the Co 2+ /Co 3+ redox cycling within Co 3 O 4 for efficient multi-enzymatic ROS scavenging. Furthermore, transcriptomic analysis and literature evidence suggest that the released Co 2+ 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 Co 3 O 4 @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.