Reactive Oxygen Species- and Cell-Free DNA-Scavenging Mn3O4 Nanozymes for Acute Kidney Injury Therapy

Longxiyu Meng; Jiayuan Feng; Jie Gao; Yihong Zhang; Wenjing Mo; Xiaozhi Zhao; Hui Wei; Hongqian Guo

doi:10.1021/acsami.2c16305

Reactive Oxygen Species- and Cell-Free DNA-Scavenging Mn₃O₄ Nanozymes for Acute Kidney Injury Therapy

ACS Appl Mater Interfaces. 2022 Nov 16;14(45):50649-50663. doi: 10.1021/acsami.2c16305. Epub 2022 Nov 5.

Authors

Longxiyu Meng¹, Jiayuan Feng², Jie Gao¹, Yihong Zhang², Wenjing Mo³, Xiaozhi Zhao¹, Hui Wei^{2

4}, Hongqian Guo¹

Affiliations

¹ Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Institute of Urology Nanjing University, Nanjing, Jiangsu 210008, China.
² 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 210093, China.
³ Department of Urology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210008, China.
⁴ State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing, Jiangsu 210023 China.

PMID: 36334088
DOI: 10.1021/acsami.2c16305

Abstract

Reactive oxygen species (ROS) scavenging therapy toward acute kidney injury (AKI) is promising, but no effective ROS scavenging drug has been developed yet. Moreover, cell-free DNA (cfDNA) is also involved in AKI, but the corresponding therapies have not been well developed. To tackle these challenges, Mn₃O₄ nanoflowers (Nfs) possessing both ROS and cfDNA scavenging activities were developed for better AKI protection as follows. First, Mn₃O₄ Nfs could protect HK2 cells through cascade ROS scavenging (dismutating ^·O₂^- into H₂O₂ by superoxide dismutase-like activity and then decomposing H₂O₂ by catalase-like activity). Second, Mn₃O₄ Nfs could efficiently adsorb cfDNA and then decrease the inflammation caused by cfDNA. Combined, remarkable therapeutic efficacy was achieved in both cisplatin-induced and ischemia-reperfusion AKI murine models. Furthermore, Mn₃O₄ Nfs could be used for the T₁-MRI real-time imaging of AKI. This study not only offered a promising treatment for AKI but also showed the translational potential of nanozymes.

Keywords: Mn3O4 nanoflowers; acute kidney injury; cell-free DNA; nanozymes; reactive oxygen species.

MeSH terms

Acute Kidney Injury* / drug therapy
Animals
Cell-Free Nucleic Acids*
Hydrogen Peroxide
Kidney
Mice
Reactive Oxygen Species
Reperfusion Injury* / drug therapy
Superoxide Dismutase

Substances

Reactive Oxygen Species
Hydrogen Peroxide
Cell-Free Nucleic Acids
Superoxide Dismutase