Montmorillonite Modulates Manganese d‐Band Center to Enhance Cascade Reaction Activity Against Inflammatory Bowel Disease

Abstract Antioxidant cascade nanozymes demonstrate significant potential for treating inflammatory bowel disease (IBD) by eliminating excess reactive oxygen species (ROS). However, developing oral antioxidant nanozymes with stable and efficient superoxide dismutase‐catalase (SOD‐CAT) cascade activity remains challenging. Herein, montmorillonite (MMT) is employed to modulate the upward shift of the MnO _2‐x d‐band center, thereby enhancing its SOD‐CAT activity and stability. Both experimental and theoretical analyses reveal that the strong interfacial interaction between MMT and MnO _2‐x improves stability, reduces the oxygen vacancy formation energy of MnO _2‐x , and elevates the Mn d‐band center. This upward shift enhances the adsorption of key intermediates, such as *OH and *O ₂ , in the SOD and CAT reaction pathways, which in turn lowers the energy barrier of the rate‐determining step. MnO _2‐x @MMT effectively scavenges intracellular ROS through the SOD‐CAT cascade reaction. Transcriptomic analysis further elucidates the molecular mechanisms through which MnO _2‐x @MMT alleviates cellular oxidative stress by activating autophagy and mitophagy pathways. Furthermore, MnO _2‐x @MMT accumulates at the site of enteritis via electrostatic adsorption, exerting antioxidant therapeutic effects and facilitating the restoration of intestinal microecology. Collectively, utilizing minerals to modulate the upward shift of the antioxidant cascade nanozyme d‐band center offers novel insights for the design of materials targeting IBD.