Enzymes assembled pickering emulsion as self-cascade bioreactor to reprogram inflammatory microenvironment for gouty...

Gouty arthritis (GA) is characterized by the deposition of monosodium urate (MSU) crystals within synovial joints, triggering a vicious cycle of intense inflammation and progressive tissue damage. Although co-delivery of uricase (URI) and catalase (CAT) has shown promise, its clinical translation is hampered by inefficient MSU dissolution and inadequate suppression of the inflammatory cascade.

We constructed a Pickering emulsion-based cascade bioreactor (PEBR) that spatially confines URI and CAT at the oil-water interface, driving the synchronized degradation of MSU crystals and its by-product (H₂O₂) through the efficient transfer of intermediates. Mannose ligands on the droplet surface enable active targeting of inflammatory macrophages, while methotrexate (MTX) sequestered in the oil core scavenges oxidative stress and provides localized anti-inflammatory effects.

A single intra-articular injection of PEBR selectively reprogrammed synovial macrophages toward the anti-inflammatory M2 phenotype in an MSU-induced mouse GA model, markedly attenuating the release of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and reversing pathological joint damage. Overall, by integrating targeted drug delivery, multi-enzyme catalysis, and immunomodulation into one modular platform, PEBR offers an elegant, adaptable, and clinically translatable strategy for precision therapy of GA.