Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction
Cardiovascular disease remains a leading cause of mortality, highlighting the critical need for novel therapeutic strategies. RNA-based therapeutics, including siRNA and mRNA, offer promising approaches for cardiac diseases, yet their clinical application is limited by low heart specificity and subo...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-10-01
|
| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425007756 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849233581315981312 |
|---|---|
| author | Xinming Wang Yiming Zhong Bei Qian Shixing Huang Qiang Long Haonan Zhang Qiang Zhao Xiaofeng Ye |
| author_facet | Xinming Wang Yiming Zhong Bei Qian Shixing Huang Qiang Long Haonan Zhang Qiang Zhao Xiaofeng Ye |
| author_sort | Xinming Wang |
| collection | DOAJ |
| description | Cardiovascular disease remains a leading cause of mortality, highlighting the critical need for novel therapeutic strategies. RNA-based therapeutics, including siRNA and mRNA, offer promising approaches for cardiac diseases, yet their clinical application is limited by low heart specificity and suboptimal delivery methods. Lipid nanoparticles (LNPs) are widely used for RNA delivery but often accumulate in non-cardiac tissues, reducing their effectiveness. To address this, an extracellular matrix (ECM)-LNP composite is developed for targeted RNA delivery to the myocardium. The LNPs are conjugated to the ECM scaffold to enhance RNA retention. In vivo experiments demonstrate effective mRNA delivery and expression within the heart, with preferential targeting towards immune cells. Epidermal growth factor receptor (EGFR), a key regulator of cell proliferation and inflammation, is found to affect macrophage polarization in this study. The therapeutic potential of EGFR siRNA delivered via ECM-LNP composite is further explored in a mouse model of myocardial infarction (MI). Results indicate that ECM-siEGFR@LNP reduces cardiac fibrosis and promotes M2 macrophage polarization. This effect is associated with down-regulation of the EGFR-AKT signaling pathway. In conclusion, this study presents an injectable platform for heart-specific RNA delivery and sheds light on the role of EGFR signaling in the cardiac repair process. |
| format | Article |
| id | doaj-art-df92f77e1bb442cca9671320fa7c58cb |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-df92f77e1bb442cca9671320fa7c58cb2025-08-20T05:07:29ZengElsevierMaterials Today Bio2590-00642025-10-013410220510.1016/j.mtbio.2025.102205Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarctionXinming Wang0Yiming Zhong1Bei Qian2Shixing Huang3Qiang Long4Haonan Zhang5Qiang Zhao6Xiaofeng Ye7Corresponding author.; Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaCorresponding author.; Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaCorresponding author.; Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaCardiovascular disease remains a leading cause of mortality, highlighting the critical need for novel therapeutic strategies. RNA-based therapeutics, including siRNA and mRNA, offer promising approaches for cardiac diseases, yet their clinical application is limited by low heart specificity and suboptimal delivery methods. Lipid nanoparticles (LNPs) are widely used for RNA delivery but often accumulate in non-cardiac tissues, reducing their effectiveness. To address this, an extracellular matrix (ECM)-LNP composite is developed for targeted RNA delivery to the myocardium. The LNPs are conjugated to the ECM scaffold to enhance RNA retention. In vivo experiments demonstrate effective mRNA delivery and expression within the heart, with preferential targeting towards immune cells. Epidermal growth factor receptor (EGFR), a key regulator of cell proliferation and inflammation, is found to affect macrophage polarization in this study. The therapeutic potential of EGFR siRNA delivered via ECM-LNP composite is further explored in a mouse model of myocardial infarction (MI). Results indicate that ECM-siEGFR@LNP reduces cardiac fibrosis and promotes M2 macrophage polarization. This effect is associated with down-regulation of the EGFR-AKT signaling pathway. In conclusion, this study presents an injectable platform for heart-specific RNA delivery and sheds light on the role of EGFR signaling in the cardiac repair process.http://www.sciencedirect.com/science/article/pii/S2590006425007756Localized deliverysiRNA therapyExtracellular matrix-lipid nanoparticle compositeMyocardial infarctionEpidermal growth factor receptor |
| spellingShingle | Xinming Wang Yiming Zhong Bei Qian Shixing Huang Qiang Long Haonan Zhang Qiang Zhao Xiaofeng Ye Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction Materials Today Bio Localized delivery siRNA therapy Extracellular matrix-lipid nanoparticle composite Myocardial infarction Epidermal growth factor receptor |
| title | Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction |
| title_full | Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction |
| title_fullStr | Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction |
| title_full_unstemmed | Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction |
| title_short | Self-assembled extracellular matrix-lipid nanoparticle composite for site-specific siRNA delivery to improve cardiac repair post-myocardial infarction |
| title_sort | self assembled extracellular matrix lipid nanoparticle composite for site specific sirna delivery to improve cardiac repair post myocardial infarction |
| topic | Localized delivery siRNA therapy Extracellular matrix-lipid nanoparticle composite Myocardial infarction Epidermal growth factor receptor |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007756 |
| work_keys_str_mv | AT xinmingwang selfassembledextracellularmatrixlipidnanoparticlecompositeforsitespecificsirnadeliverytoimprovecardiacrepairpostmyocardialinfarction AT yimingzhong selfassembledextracellularmatrixlipidnanoparticlecompositeforsitespecificsirnadeliverytoimprovecardiacrepairpostmyocardialinfarction AT beiqian selfassembledextracellularmatrixlipidnanoparticlecompositeforsitespecificsirnadeliverytoimprovecardiacrepairpostmyocardialinfarction AT shixinghuang selfassembledextracellularmatrixlipidnanoparticlecompositeforsitespecificsirnadeliverytoimprovecardiacrepairpostmyocardialinfarction AT qianglong selfassembledextracellularmatrixlipidnanoparticlecompositeforsitespecificsirnadeliverytoimprovecardiacrepairpostmyocardialinfarction AT haonanzhang selfassembledextracellularmatrixlipidnanoparticlecompositeforsitespecificsirnadeliverytoimprovecardiacrepairpostmyocardialinfarction AT qiangzhao selfassembledextracellularmatrixlipidnanoparticlecompositeforsitespecificsirnadeliverytoimprovecardiacrepairpostmyocardialinfarction AT xiaofengye selfassembledextracellularmatrixlipidnanoparticlecompositeforsitespecificsirnadeliverytoimprovecardiacrepairpostmyocardialinfarction |