Assembly of Ceria-Nrf2 Nanoparticles As Macrophage-targeting ROS Scavengers Protects Against Myocardial Infarction

Overview

Journal Front Pharmacol

Date 2025 Jan 27

PMID 39867660

Authors

Wenjing Liao

Jinduan Lin

Wenli Wang

Ming Zhang

Yanfang Chen

Xin Li

Huan Liu

Pan Xia Wang

Guojun Zhao

Jijun Fu

Xiaoqian Wu

Affiliations

Soon will be listed here.

Abstract

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide, and mitigating oxidative stress is crucial in managing MI. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in combating oxidative stress and facilitating cardiac remodeling post-MI. Here, we engineered Cerium oxide (CeO) nanoparticle-guided assemblies of ceria/Nrf2 nanocomposites to deliver Nrf2 plasmids. The CeO/Nrf2 nanocomposites effectively activated the Nrf2/antioxidant response element (ARE) signaling pathway both and . In a mouse MI model induced by permanent ligation of the left anterior descending artery (LAD), CeO/Nrf2 nanocomposites were administered via tail vein injection, predominantly targeting circulating monocytes and macrophages which will be recruited to the heart post MI due to the acute inflammatory response. We demonstrated that CeO/Nrf2 nanocomposites alleviated cardiac systolic dysfunction and significantly reduced infarct size and scar fibrosis post-MI. Furthermore, CeO/Nrf2 nanocomposites effectively mitigated MI-induced oxidative stress and downregulated Nrf2-regulated inflammatory genes (tumor necrosis factor-α, IL-6, and inducible nitric oxide synthase), thereby reducing cardiomyocyte apoptosis. These findings indicate that CeO/Nrf2 nanocomposites significantly enhance Nrf2 signaling activation and confer protection against MI. This study identifies CeO/Nrf2 nanocomposites as a promising strategy for post-MI therapy.

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