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 abnormal deposition of monosodium urate (MSU) crystals in articular structures. Current clinical medications can only alleviate the inflammation caused by the acute GA temporarily, but have no solution to the deposition of MSU. To surmount this, 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 bond to form the platform (termed UBC). This way, the platform could not only directly eliminate the MSU, but also release the therapeutic gas hydrogen sulfide (H2S) triggered by the toxic by-product of UOx catalysis, hydrogen peroxide (H2O2). Synergized with curcumin, the inflammation could be effectively suppressed. In vivo experiments on an acute GA murine model also validated the potent therapeutic effect of the platform, mainly due to the synergistic effect 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 and other biomolecules.