Osteoarthritis (OA) is driven by a vicious cycle of inflammation and reactive oxygen species (ROS). Although cobalt-based metal-organic frameworks (MOF) nanoenzymes are potent hydrogen peroxide enzymes (CAT) mimics, their therapeutic effects are limited due to their inherent weak superoxide dismutase (SOD)-like activity, which prevents the complete clearance of all-chain ROS. We addressed this imbalance through an innovative "pre-embedding/activation" strategy. This method involves pre-embedding Zn2+ into the cobalt-based framework to create stable and activatable precursors. Subsequently, dopamine (DA)-driven "activation" reshapes the potential zinc/iron-nitrogen coordination sites, achieving efficient SOD-to-CAT catalytic inheritance through synergistic amplification of SOD-like activity, enabling seamless elimination of the entire ROS cascade. This powerful clearance ability restores mitochondrial function and reprograms macrophages to an anti-inflammatory M2 phenotype by inhibiting ROS-mediated S100A8/NF-κB signaling axis and its destructive positive feedback loop. The resulting immune modulation translates into profound therapeutic effects in a rat osteoarthritis model, promoting chondrocyte synthesis for significant cartilage repair, while inhibiting peripheral nerve sensitization and providing sustained pain relief. Therefore, our research establishes nanoscale interface reconstruction as a powerful and rational platform for engineering complex catalytic relays within nanoenzymes, applicable to advanced biomedical applications. This study was published in Advanced Materials under the title "Unlocking an Efficient SOD-to-CAT Catalytic Relay in a MOF Nanozyme via Dopamine-Driven Interfacial Nanoreconstruction for Osteoarthritis Therapy".
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DOI: 10.1002/adma.72747