Artificial Metalloenzyme-Based Enzyme Replacement Therapy for the Treatment of Hyperuricemia

Enzyme replacement therapy (ERT) holds great potential for treating enzyme deficiency related diseases. However, the enzymic vulnerability and the undesirable toxic side effects have strongly limited its clinical applications. Here a novel artificial metalloenzyme-based ERT with significant self-protection and toxic self-cleaning ability is developed for the treatment of hyperuricemia. The uricase and platinum nanoparticles (PtNPs) are closely confined in the pores of mesoporous silica nanoparticles and encapsulated within a silica defense layer to form a tandem catalytic system. This artificial metalloenzyme keeps a high uric acid (UA) degradation activity, as well as a strong resistance capability toward various insults, such as pH, high temperature, and protease. Besides, the H2O2 produced by UA can be simultaneously eliminated by the PtNPs, resulting in significant improvement on the mammalian cell viability. In vivo studies display prominent therapy effect and no obvious side effects during the treatment of hyperuricemia mice using this artificial metalloenzyme. These results provide new insights into development of efficient and friendly enzyme replacement therapy.