State Key Laboratory of Pharmaceutical Biotechnology, Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, People's Republic of China.
Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing National Laboratory of Microstructures, Jiangsu Key Laboratory of Artificial Functional Materials, Nanjing University, Nanjing, Jiangsu 210023, People's Republic of China.
Nano Lett. 2022 Jan 12;22(1):508-516. doi: 10.1021/acs.nanolett.1c04454. Epub 2021 Dec 30.
Uricase-based therapies are limited for gout partially due to the accumulation of HO in an arthrosis environment with slow metabolism. To tackle this limitation, previous studies adopted a cascade reaction between the degradation of uric acid (UA) and timely elimination of HO using complicated composites of uricase and catalase (CAT)/CAT-like nanozyme. Herein, the self-cascade nanozyme Pt/CeO with high efficiency toward simultaneous UA degradation and HO elimination is demonstrated on the basis of both uricase- and CAT-like activities in Pt, Ir, Rh, and Pd platinum-group metals. With an optimized molar ratio of Pt and CeO, Pt/CeO (1/5) not only does better in degrading UA but also has excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavenging activities. In monosodium urate (MSU)-induced acute gout rats, Pt/CeO nanozyme markedly alleviates pain along with joint edema, thus improving gait claudication and tissue inflammation. These results provide novel insights into strategies of an efficient enzyme-mimetic treatment for gout.
基于尿酸酶的疗法在治疗痛风方面存在一定局限性，部分原因是尿酸酶在关节炎环境中代谢缓慢，导致 HO 积累。为了解决这一限制，先前的研究采用尿酸（UA）降解和 HO 及时消除的级联反应，使用尿酸酶和过氧化氢酶（CAT）/CAT 样纳米酶的复杂复合材料。在此基础上，基于铂族金属中的尿酸酶和 CAT 样活性，展示了高效的同时降解 UA 和消除 HO 的自级联纳米酶 Pt/CeO。通过优化 Pt 和 CeO 的摩尔比，Pt/CeO（1/5）不仅在降解 UA 方面表现更好，而且具有优异的活性氧（ROS）和活性氮（RNS）清除活性。在单钠尿酸盐（MSU）诱导的急性痛风大鼠中，Pt/CeO 纳米酶显著缓解疼痛和关节肿胀，从而改善步态跛行和组织炎症。这些结果为痛风的高效酶模拟治疗策略提供了新的思路。
