Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction
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...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1503757/full |
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| author | Wenjing Liao Jinduan Lin Wenli Wang Ming Zhang Yanfang Chen Xin Li Huan Liu Pan Xia Wang Guojun Zhao Jijun Fu Xiaoqian Wu |
| author_facet | Wenjing Liao Jinduan Lin Wenli Wang Ming Zhang Yanfang Chen Xin Li Huan Liu Pan Xia Wang Guojun Zhao Jijun Fu Xiaoqian Wu |
| author_sort | Wenjing Liao |
| collection | DOAJ |
| description | 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 (CeO2) nanoparticle-guided assemblies of ceria/Nrf2 nanocomposites to deliver Nrf2 plasmids. The CeO2/Nrf2 nanocomposites effectively activated the Nrf2/antioxidant response element (ARE) signaling pathway both in vivo and in vitro. In a mouse MI model induced by permanent ligation of the left anterior descending artery (LAD), CeO2/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 CeO2/Nrf2 nanocomposites alleviated cardiac systolic dysfunction and significantly reduced infarct size and scar fibrosis post-MI. Furthermore, CeO2/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 CeO2/Nrf2 nanocomposites significantly enhance Nrf2 signaling activation and confer protection against MI. This study identifies CeO2/Nrf2 nanocomposites as a promising strategy for post-MI therapy. |
| format | Article |
| id | doaj-art-7c0c58a41dfb4c669dfb8b39ec59771f |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-7c0c58a41dfb4c669dfb8b39ec59771f2025-08-20T02:45:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15037571503757Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarctionWenjing Liao0Jinduan Lin1Wenli Wang2Ming Zhang3Yanfang Chen4Xin Li5Huan Liu6Pan Xia Wang7Guojun Zhao8Jijun Fu9Xiaoqian Wu10The Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaThe Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaThe Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaThe Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaDepartment of Pharmacy, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaThe Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaState Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, ChinaThe Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaThe Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaThe Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaThe Sixth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target and Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, The Fifth Affiliated Hospital, Guangzhou, ChinaMyocardial 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 (CeO2) nanoparticle-guided assemblies of ceria/Nrf2 nanocomposites to deliver Nrf2 plasmids. The CeO2/Nrf2 nanocomposites effectively activated the Nrf2/antioxidant response element (ARE) signaling pathway both in vivo and in vitro. In a mouse MI model induced by permanent ligation of the left anterior descending artery (LAD), CeO2/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 CeO2/Nrf2 nanocomposites alleviated cardiac systolic dysfunction and significantly reduced infarct size and scar fibrosis post-MI. Furthermore, CeO2/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 CeO2/Nrf2 nanocomposites significantly enhance Nrf2 signaling activation and confer protection against MI. This study identifies CeO2/Nrf2 nanocomposites as a promising strategy for post-MI therapy.https://www.frontiersin.org/articles/10.3389/fphar.2024.1503757/fullmyocardial infarctionceria nanoparticlesNrf2oxidative stressinflammation |
| spellingShingle | Wenjing Liao Jinduan Lin Wenli Wang Ming Zhang Yanfang Chen Xin Li Huan Liu Pan Xia Wang Guojun Zhao Jijun Fu Xiaoqian Wu Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction Frontiers in Pharmacology myocardial infarction ceria nanoparticles Nrf2 oxidative stress inflammation |
| title | Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction |
| title_full | Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction |
| title_fullStr | Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction |
| title_full_unstemmed | Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction |
| title_short | Assembly of ceria-Nrf2 nanoparticles as macrophage-targeting ROS scavengers protects against myocardial infarction |
| title_sort | assembly of ceria nrf2 nanoparticles as macrophage targeting ros scavengers protects against myocardial infarction |
| topic | myocardial infarction ceria nanoparticles Nrf2 oxidative stress inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1503757/full |
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