Curcumin driven formation of self-cascade nanoclusters from urate oxidase-H₂S donor conjugates for acute gouty arthritis alleviation

Gouty arthritis (GA) is a common arthritis characterized by chronic inflammation and monosodium urate (MSU) crystal deposition in articular structures. Current clinical medications mainly target to alleviate the inflammation, but do less to the deposited MSU. Although administration of urate oxidase (UOx) could degrade the MSU, the toxic by-product hydrogen peroxide (H₂O₂) generated during the degradation would aggravate the inflammation. To surmount this, we developed a smart stimuli-responsive drug delivery platform (termed UBC) for the treatment of acute GA, where urate oxidase (UOx) was initially modified with the phenylboronic acid-based self-immolative thiocarbamate through nucleophilic substitution, and then co-assembled with curcumin through boronate bonds. This way, the platform could not only directly eliminate MSU, but also release the therapeutic agents, hydrogen sulfide (H₂S) gas and curcumin, triggered by the toxic by-product H₂O₂ during UOx catalysis. Thus, the inflammation could be effectively restrained by the in situ co-delivery of H₂S and curcumin. We believe this strategy provides a novel approach for the treatment of inflammation-related diseases and novel insight into the construction of multi-functional therapeutic nanomaterials from enzymes or other biomolecules.