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 HO 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 HO. 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.