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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 catalase (CAT) mimics, their therapeutic efficacy is limited by their inherently weak superoxide dismutase (SOD)-like activity, which prevents the complete clearance of the entire ROS cascade. Here, we address this imbalance through an innovative "pre-embedding/activation" strategy. This approach involves pre-embedding Zn2+ into the cobalt-based framework to create stable and activatable precursors. Subsequently, the "activation" driven by dopamine (DA) reshapes the potential zinc/bismuth coordination sites, achieving efficient SOD-to-CAT catalytic relay through synergistic amplification of SOD-like activity, enabling seamless elimination of the entire ROS cascade. This powerful clearance ability inhibits the ROS-mediated S100A8/NF-κB signaling axis and its destructive positive feedback loop, restoring mitochondrial function and reprogramming macrophages to an anti-inflammatory M2 phenotype. The resulting immunomodulation translates into profound therapeutic effects in a rat osteoarthritis model, promoting chondrocyte synthesis for significant cartilage repair, while inhibiting the sensitization of peripheral nerves, thereby 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".
Reference News: DOI: 10.1002/adma.72747
