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Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes

文献类型：期刊论文

作者Zhuo, Yan6,7,8; Luo, Zhen5; Zhu, Zhu4,7,8; Wang, Jie3,7,8; Li, Xiang2,7,8; Zhang, Zhuan7,8; Guo, Cong2,7,8; Wang, Bingqi2,7,8; Nie, Di2,7,8; Gan, Yong1,2,7,8
刊名NATURE NANOTECHNOLOGY
出版日期2024-09-19
页码19
ISSN号1748-3387
DOI10.1038/s41565-024-01785-0
通讯作者Gan, Yong(ygan@simm.ac.cn) ; Hu, Guoqing(ghu@zju.edu.cn) ; Yu, Miaorong(mryu@simm.ac.cn)
英文摘要Efficient cytosolic delivery is a significant hurdle when using short interfering RNA (siRNA) in therapeutic applications. Here we show that cholesterol-rich exosomes are prone to entering cancer cells through membrane fusion, achieving direct cytosolic delivery of siRNA. Molecular dynamics simulations suggest that deformation and increased contact with the target cell membrane facilitate membrane fusion. In vitro we show that cholesterol-enriched milk-derived exosomes (MEs) achieve a significantly higher gene silencing effect of siRNA, inducing superior cancer cell apoptosis compared with the native and cholesterol-depleted MEs, as well as conventional transfection agents. When administered orally or intravenously to mice bearing orthotopic or subcutaneous tumours, the cholesterol-enriched MEs/siRNA exhibit antitumour activity superior to that of lipid nanoparticles. Collectively, by modulating the cholesterol content of exosome membranes to facilitate cell entry via membrane fusion, we provide a promising approach for siRNA-based gene therapy, paving the way for effective, safe and simple gene therapy strategies. Researchers demonstrate that cholesterol-enriched exosomes can deliver siRNA directly into cancer cells, bypassing normal cellular barriers and significantly enhancing gene silencing. This offers a more effective method for gene therapy applications.
WOS关键词THERAPY
资助项目National Natural Science Foundation of China (National Science Foundation of China)[82025032] ; National Science Fund of Distinguished Young Scholars[2022YFA1203200] ; National Key Research and Development Program of China[82073773] ; National Natural Science Foundation of China[2022QNRC001] ; Young Elite Scientists Sponsorship Program by CAST[ZDBS-ZRKJZ-TLC005] ; Young Elite Scientists Sponsorship Program by CAST[NCTIB2022HS01006] ; Key Research Program of Chinese Academy of Sciences[23HC1401200] ; Shanghai Action Plan for Science, Technology and Innovation[SIMM0220232001] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences ; Shanghai Advanced Research Institute, Chinese Academy of Sciences, China
WOS研究方向Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001321097400002
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/313669]  
专题新药研究国家重点实验室
通讯作者Gan, Yong; Hu, Guoqing; Yu, Miaorong
作者单位1.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai, Peoples R China
4.Henan Univ, Sch Pharm, Kaifeng, Peoples R China
5.Zhejiang Univ, Dept Engn Mech, State Key Lab Fluid Power & Mechatron Syst, Hangzhou, Peoples R China
6.Nanchang Univ, Jiangxi Med Coll, Sch Pharm, Nanchang, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai, Peoples R China
8.Chinese Acad Sci, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Zhuo, Yan,Luo, Zhen,Zhu, Zhu,et al. Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes[J]. NATURE NANOTECHNOLOGY,2024:19.
APA Zhuo, Yan.,Luo, Zhen.,Zhu, Zhu.,Wang, Jie.,Li, Xiang.,...&Yu, Miaorong.(2024).Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes.NATURE NANOTECHNOLOGY,19.
MLA Zhuo, Yan,et al."Direct cytosolic delivery of siRNA via cell membrane fusion using cholesterol-enriched exosomes".NATURE NANOTECHNOLOGY (2024):19.

入库方式： OAI收割

来源：上海药物研究所

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