An engineered sweeper with multi-stage intervention against uric acid, crystals, and inflammation for gouty arthritis therapy.

Gouty arthritis (GA) is an inflammatory joint disease driven by hyperuricemia and deposition of monosodium urate (MSU) crystals. Current therapeutic strategies primarily focus on the intervention of serum uric acid (UA) or inflammation, while neglecting the crucial process of MSU crystal formation. To address this gap, we employed a top-down therapeutic approach and developed a multifunctional "sweeper" termed UCCN. It synergistically reduced UA level while avoiding H2O2 accumulation through the degradable synergy of hollow cerium oxide nanostructures (hCeO2) and encapsulated urate oxidase. Moreover, the outer chondroitin sulfate layer, which is functionalized with o-phenylenediamine moieties, not only inhibits MSU crystallization but also scavenges pro-inflammatory mediator nitric oxide. Thus, UCCN was evidenced to effectively inhibit the formation of MSU crystals, suppress inflammation, and mitigate osteoclast hyperactivity to alleviate GA symptoms. It is believed that this work establishes a comprehensive multi-stage intervention strategy for GA treatment and provides insights for managing other inflammatory diseases.