Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy

Author:

Liu Wanling1,Zhang Yihong1,Wei Gen1,Zhang Minxuan1,Li Tong1,Liu Quanyi23,Zhou Zijun1,Du Yan23,Wei Hui14ORCID

Affiliation:

1. College of Engineering and Applied Sciences Nanjing National Laboratory of Microstructures Jiangsu Key Laboratory of Artificial Functional Materials Nanjing University 210023 Nanjing Jiangsu China

2. State Key Laboratory of Electroanalytical Chemistry Changchun Institute of Applied Chemistry Chinese Academy of Sciences 130022 Jilin Changchun China

3. School of Applied Chemistry and Engineering University of Science and Technology of China 230026 Hefei Anhui 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 210023 Nanjing Jiangsu China

Abstract

AbstractSenescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase‐ and glutathione peroxidase‐like activities, named MSe1, is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low‐density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E‐deficient (ApoE−/−) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Priority Academic Program Development of Jiangsu Higher Education Institutions

Fundamental Research Funds for the Central Universities

Publisher

Wiley

Subject

General Chemistry,Catalysis

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