AUTHOR=Hou Xinyue , Shi Jianxiang , Zhang Jie , Wang Zhigang , Zhang Sen , Li Ruifeng , Jiang Wei , Huang Tingting , Guo Jiancheng , Shang Wenjun 

TITLE=Treatment of Acute Kidney Injury Using a Dual Enzyme Embedded Zeolitic Imidazolate Frameworks Cascade That Catalyzes In Vivo Reactive Oxygen Species Scavenging

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=Volume 9 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2021.800428

DOI=10.3389/fbioe.2021.800428

ISSN=2296-4185

ABSTRACT=Abstract
Significant advances have been made in recent years for the utilization of natural enzymes with antioxidant properties for the treatment of acute kidney injury (AKI). Owing to their limited cellular uptake, poor pharmacokinetic properties, and suboptimal stability, however, these enzymes have been of limited clinical utility. Herein, we employed a novel biomimetic mineralization approach to encapsulate catalase (CAT) and superoxide dismutase (SOD) in a zeolitic imidazolate framework-8 (ZIF-8), after which this obtained SOD@CAT@ZIF-8 complex was anchored with MPEG2000-COOH to yield an MPEG2000-SOD@CAT@ZIF-8 (PSCZ) composite. This composite was then utilized as a stable tool with antioxidant properties for the integrated cascade-based treatment of AKI, remarkably improved intracellular enzyme delivery. This dual-enzyme-embedded metal-organic framework was able to effectively scavenge reactive oxygen species synergistically. In conclusion, the ZIF-8-based “armor plating” represents an effective means of shielding enzymes with improved therapeutic utility to guide the precision medicine-based treatment of AKI.