Cascade Nanozyme‐Catalyzed Tophi Dissolution and ROS Scavenging for Anti‐Inflammatory Therapy in Gouty Arthritis

ABSTRACT Tophi, inflammatory granulomas formed by intra‐articular monosodium urate (MSU) crystal deposition, remain challenging due to limited drug efficacy. While arthroscopic surgery removes tophi rapidly, mechanical debridement risks injury, and intraoperative MSU release can trigger severe oxidative stress induced inflammatory storm. To overcome this, we developed a cascade nanozyme, Ce‐MOF@Pt, enabling synergistic MSU clearance and ROS scavenging for MSU‐induced gouty arthritis. Pt nanoparticles possess oxidase (OXD)‐like activity, dissolving deeply embedded MSU crystals without mechanical injury and incidentally producing anti‐inflammatory allantoin. The Ce‐MOF matrix supports Pt and duplicates catalase (CAT)/superoxide dismutase (SOD)‐like activities, cascading H ₂ O ₂ decomposition and MSU‐induced ROS elimination. As UA degradation elevates the local pH values, its dominant activity intelligently switches from OXD‐like to SOD‐like mode, while the CAT‐like activity remains consistently high, ensuring continuous clearance of the H ₂ O ₂ byproduct and offering integrated anti‐oxidative therapy. In vitro, Ce‐MOF@Pt reduced inflammation via ROS scavenging and macrophage reprogramming. In vivo, it alleviated pain symptoms and joint inflammation in MSU‐induced gouty arthritis mice. Transcriptomics revealed Ce‐MOF@Pt mitigated the inflammatory storm by alleviating endoplasmic reticulum stress. This novel Ce‐MOF@Pt strategy offers minimally invasive tophi dissolution and prevents MSU‐induced inflammation, providing a promising therapeutic approach for tophi.