Albumin Corona-Coated Nanoscale Metal–Organic Framework for Enzyme-Mediated Cascade Metabolization of Uric Acid in Hyperuricemia

Hyperuricemia, characterized by elevated uric acid levels, is the primary cause of gout. Recombinant uricase is one of the last-resort therapies but generates unwanted pro-inflammatory H 2 O 2 and anti-uricase antibodies. In this work, we developed an albumin corona-coated enzyme-loaded zeolitic imidazolate framework (UCZIF) to sustainably maintain low blood uric acid level without producing H 2 O 2 . The corona coating not only preserves loaded enzymes but also reduces macrophage phagocytosis by 73.4% compared to free uricase. In addition, the uptake level of UCZIF by dendritic cells is reduced by 74.1%, and the maturation of dendritic cells is inhibited by 35.4% compared to free uricase. Animal experiments demonstrate that albumin corona-coated UCZIF effectively lowers blood uric acid level in both acute and diet-induced chronic hyperuricemia models with significantly increasing the half-life of uricase. Furthermore, compared to the generation of anti-uricase antibodies during standalone uricase treatment, the levels of anti-uricase immunoglobulins are significantly reduced by 65.5% (immunoglobulin M) and 76.3% (immunoglobulin G) with repeated administration of albumin corona-coated UCZIF. Overall, this albumin corona-coated nanoscale metal–organic framework offers a promising approach to minimize the immunogenicity induced by exogenous enzymes and further safely reduce uric acid levels in the treatment of hyperuricemia.