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Adv. Healthc. Mater., Apr 07 2025, | https://doi.org/10.1002/adhm.202404398
Developing Therapeutically Enhanced Extracellular Vesicles for Atherosclerosis Therapy
Neil Patel 1, Elijah Avery 1, Yi Huang 1, Eun Ji Chung 1,2,3,4,5,6,7
1Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.
2Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
3Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA.
4Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
5Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.
6Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
7Bridge Institute, University of Southern California, Los Angeles, CA, USA.
Corresponding Author: Eun Ji Chung
1Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.
2Department of Medicine, Division of Nephrology and Hypertension, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
3Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA.
4Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
5Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.
6Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
7Bridge Institute, University of Southern California, Los Angeles, CA, USA.
Corresponding Author: Eun Ji Chung
Abstract
Atherosclerosis is a chronic condition and the leading cause of death worldwide. While statin therapy is the clinical standard, many patients still experience acute cardiovascular events. To develop better therapies, the group previously delivered microRNA-145 (miR-145) via micellar nanoparticles to vascular smooth muscle cells (VSMCs) to inhibit atherosclerosis. However, for chronic diseases requiring repeat dosing, synthetic nanoparticles have drawbacks such as immunogenic response and low delivery efficiency. To meet this challenge, therapeutically enhanced extracellular vesicles (EVs) are engineered as a biologically-derived nanoparticle modality to mitigate atherosclerosis. A novel strategy is employed to load miR-145 into EVs using ExoMotifs-short miRNA sequences that facilitate miR cargo loading. EVs are further functionalized with a monocyte chemoattractant 1 (MCP-1) peptide, which binds to C-C chemokine receptor 2 upregulated in pathogenic VSMCs. Mouse aortic smooth muscle cell MCP-1-miR-145 EVs restored VSMC gene expression and function in vitro. Moreover, compared to miR-145-loaded synthetic nanoparticles, MCP-1-miR-145 EVs exerted similar therapeutic effects but with 25,000x less miR-145 cargo. Lastly, MCP-1-miR-145 EVs inhibited plaque growth in mid-stage ApoE-/- atherosclerotic mice at a miR-145 dose 5000x less than synthetic nanoparticles. Collectively, it is demonstrated that genetic engineering of VSMCs with miR-145 produces therapeutically boosted EVs that reduce atherosclerosis plaque burden.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-05-09)
- 국외 연구진
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