An antioxidant system through conjugating superoxide dismutase onto metal-organic framework for cardiac repair

Jiacheng Guo; Zhenzhen Yang; Yongzheng Lu; Chunyan Du; Chang Cao; Bo Wang; Xiaoting Yue; Zenglei Zhang; Yanyan Xu; Zhen Qin; Tingting Huang; Wei Wang; Wei Jiang; Jinying Zhang; Junnan Tang

doi:10.1016/j.bioactmat.2021.08.019

An antioxidant system through conjugating superoxide dismutase onto metal-organic framework for cardiac repair

Bioact Mater. 2021 Aug 22:10:56-67. doi: 10.1016/j.bioactmat.2021.08.019. eCollection 2022 Apr.

Authors

Jiacheng Guo^{1

2}, Zhenzhen Yang³, Yongzheng Lu^{1

2}, Chunyan Du⁴, Chang Cao^{1

2}, Bo Wang^{1

2}, Xiaoting Yue^{1

2}, Zenglei Zhang^{1

2}, Yanyan Xu^{1

2}, Zhen Qin^{1

2}, Tingting Huang⁵, Wei Wang⁶, Wei Jiang⁷, Jinying Zhang^{1

2}, Junnan Tang^{1

2}

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
² Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, 450018, China.
³ Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
⁴ Laboratory Animal Center, School of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, China.
⁵ Department of Polymer Science, College of Chemistry, Jilin University, Changchun, Jilin, 130012, China.
⁶ Henan Medical Association, Zhengzhou, Henan, 450052, China.
⁷ Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450052, China.

Abstract

Acute myocardial infarction (AMI) remains a dominant origin of morbidity, mortality and disability worldwide. Increases in reactive oxygen species (ROS) are key contributor to excessive cardiac injury after AMI. Here we developed an immobilized enzyme with Superoxide Dismutase (SOD) activity cross-link with Zr-based metal-organic framework (ZrMOF) (SOD-ZrMOF) for mitigate ROS-caused injury. In vitro and in vivo evidence indicates that SOD-ZrMOF exhibits excellent biocompatibility. By efficiently scavenging ROS and suppressing oxidative stress, SOD-ZrMOF can protect the function of mitochondria, reduce cell death and alleviate inflammation. More excitingly, long-term study using an animal model of AMI demonstrated that SOD-ZrMOF can reduce the infarct area, protect cardiac function, promote angiogenesis and inhibit pathological myocardial remodeling. Therefore, SOD-ZrMOF holds great potential as an efficacious and safe nanomaterial treatment for AMI.

Keywords: Acute myocardial infarction; Immobilized enzyme; Nanomedicine; Reactive oxygen species.