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J. Extracell. Vesicles, Oct 2023, 12 (10) | https://doi.org/10.1002/jev2.12371
Engineered small extracellular vesicle-mediated NOX4 siRNA delivery for targeted therapy of cardiac hypertrophy.
Ji-Young Kang 1, Dasom Mun 1, Yumin Chun 1, Da-Seul Park 1, Hyoeun Kim 2, Nuri Yun 3, Boyoung Joung 1,4
1Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Republic of Korea.
2Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Republic of Korea.
3GNTPharma Science and Technology Center for Health, Giheung-gu, Yongin-si, Incheon, Republic of Korea.
4Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Republic of Korea.
CORRESPONDING AUTHORS : Nuri Yun, Boyoung Joung
Abstract
Small-interfering RNA (siRNA) therapy is considered a powerful therapeutic strategy for treating cardiac hypertrophy, an important risk factor for subsequent cardiac morbidity and mortality. However, the lack of safe and efficient in vivo delivery of siRNAs is a major challenge for broadening its clinical applications. Small extracellular vesicles (sEVs) are a promising delivery system for siRNAs but have limited cell/tissue-specific targeting ability. In this study, a new generation of heart-targeting sEVs (CEVs) has been developed by conjugating cardiac-targeting peptide (CTP) to human peripheral blood-derived sEVs (PB-EVs), using a simple, rapid and scalable method based on bio-orthogonal copper-free click chemistry. The experimental results show that CEVs have typical sEVs properties and excellent heart-targeting ability. Furthermore, to treat cardiac hypertrophy, CEVs are loaded with NADPH Oxidase 4 (NOX4) siRNA (siNOX4). Consequently, CEVs@siNOX4 treatment enhances the in vitro anti-hypertrophic effects by CEVs with siRNA protection and heart-targeting ability. In addition, the intravenous injection of CEVs@siNOX4 into angiotensin II (Ang II)-treated mice significantly improves cardiac function and reduces fibrosis and cardiomyocyte cross-sectional area, with limited side effects. In conclusion, the utilization of CEVs represents an efficient strategy for heart-targeted delivery of therapeutic siRNAs and holds great promise for the treatment of cardiac hypertrophy.
논문정보
- Research article
- 2023년 10월 (BRIC 등록일 2023-10-10)
- 국내 연구진
- 의약학 > 응용의학
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