Polymer-encapsulated dual-enzyme carbon dots enable self-cascaded uric acid-hydrogen peroxide metabolic cascade for targeted gout therapy

• Vitamin B12-derived carbon dots exhibit dual enzymatic activities, autonomously degrading urate crystals and neutralizing reactive oxygen species. • Nano-encapsulation enhances joint targeting and lesion accumulation in gout models, leading to enhanced therapeutic outcomes. • The nanotherapeutic strategy effectively reduces inflammation, preserves joint integrity, and shows no detectable organ toxicity. • This study presents a novel and targeted approach for gout treatment through self-sustaining detoxification loops. Gout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in joints, which triggers oxidative bursts and leads to severe inflammation. Antioxidant-based therapeutic strategies, while promising for disrupting this pathological cascade by mitigating oxidative stress, are nevertheless hampered by inherent limitations such as insufficient enzymatic activity and lack of targeting specificity. Herein, this study presents an innovative solution by engineering vitamin B 12 -derived carbon dots (CDs) with dual urate oxidase and catalase-like activities. These CDs, synthesized via hydrothermal methods, retain the bioactive cobalt-corrin core of VB 12 , enabling self-driven enzymatic reactions to sequentially degrade uric acid and scavenge hydrogen peroxide, forming an autonomous detoxification loop. In situ radical polymerization-mediated polymer encapsulation yields n(CDs) with enhanced joint-targeting capability. In MSU-induced acute gouty arthritis rat models, n(CDs) outperforms bare CDs in therapeutic efficacy, significantly reducing paw edema, preserving joint architecture in histopathological analyses, and demonstrating enhanced lesion accumulation via fluorescence imaging. This nano-platform concurrently degrades MSU crystals and neutralizes reactive oxygen species without detectable organ toxicity, establishing a promising targeted nanotherapeutic strategy for gout intervention