Synergistic Degradation of a Hyperuricemia-Causing Metabolite Using One-Pot Enzyme-Nanozyme Cascade Reactions

Secheon Jung,Inchan Kwon

doi:10.1038/srep44330

Abstract

Multi-enzyme cascade reactions are frequently found in living organisms, in particular when an intermediate should be eliminated. Recently, enzyme-mimic nanomaterials (nanozymes) received much attention for various applications, because they are usually more stable and cost-effective than enzymes. However, enzyme-nanozyme cascade reations have not been yet extensively exploited. Therefore, in this study, we investigated one-pot enzyme-nanozyme cascade reactions using urate oxidase (UOX) and catalase-mimic gold nanoparticle nanozyme (AuNP) with the ultimate goal of treatment of hyperuricemia. UOX degrades hyperuricemia-causing uric acid, but also generates hydrogen peroxide raising several health concerns. We successfully demonstrated that one-pot UOX-AuNP cascade systems degrade uric acid more than five times faster than UOX alone, by eliminating potentially cytotoxic hydrogen peroxide, similar to enzyme-enzyme reactions.

Highlights

Catalase is an enzyme that catalyzes the dissociation of hydrogen peroxide into oxygen and water
The single band was located between 25- and 37-kDa molecular weight standards, which is consistent with the expected molecular weight of urate oxidase (UOX), 33.4 kDa
The catalytic activity profile of UOX was determined at 5 nM UOX and 100 μM uric acid over a pH range of 8.0 to 9.5 (Fig. 2d)

Summary

Introduction

Catalase is an enzyme that catalyzes the dissociation of hydrogen peroxide into oxygen and water. Catalase may efficiently eliminate hydrogen peroxide generated during uric acid degradation by UOX, it has several intrinsic limitations as an enzyme, such as low stability and relatively high production cost[16]. Various nanozymes have been developed to mimic natural enzymes, including peroxidase, oxidase, superoxide dismutase, and catalase[17,18,19,20,21,22,23]. Considering the ultimate therapeutic application of UOX-nanozyme cascade system, we chose AuNPs coated with polyvinylpyrrolidone (PVP). He et al reported both PVP-coated gold nanoparticles exhibit pH-dependent catalytic activity interconversion between SOD and catalase[35]. In order to evaluate the relative performance of AuNPs coated with PVP, we compared the performance of AuNPs coated with PVP with those with other stabilizing agents including poly ethyleneglycol (PEG), citric acid (CA), and tannic acid (TA)

Methods

Results

Conclusion