Manganese-Dioxide Nanozyme and Uricase Co-Stabilized Biomimetic Microreactor Enhanced Interfacial Cascade Catalysis...

Gouty arthritis (GA) arises from monosodium urate (MSU) crystal deposition and self-perpetuating immune dysregulation. Uricase (URI)-based therapy can deplete uric acid but is limited by inefficient MSU clearance, immunogenicity, and uncontrolled inflammation. Here, we present a biomimetic microreactor (PEMU), a Pickering emulsion co-stabilized by manganese dioxide (MnO₂) nanozymes and URI, designed for integrated catalytic and immunomodulatory therapy for GA. The nanoscale proximity of the MnO₂ nanozyme and URI at the oil-water interface establishes a geometrically confined catalytic microenvironment that facilitates a rapid, self-sustaining cascade. URI oxidizes urate, producing hydrogen peroxide (H₂O₂), which is immediately decomposed in situ by the adjacent MnO₂ nanozyme through its catalase-like activity, thereby preventing H₂O₂ accumulation and oxidative damage. The rigid interface further enhances substrate enrichment and mass transfer, allowing for efficient scavenging of endogenous reactive oxygen species. Consequently, PEMU suppresses aberrant activation of the NLRP3 inflammasome and NF-κB pathways and reprograms macrophages from the pro-inflammatory M1 phenotype to the pro-resolving M2 phenotype. A single intra-articular injection of PEMU reduces MSU crystal deposition, paw edema, and tissue injury in GA mice. These findings establish enzyme-nanozyme hybrid microreactors as a comprehensive platform for reshaping the inflammatory microenvironment of GA and other inflammatory diseases.