期刊
ADVANCED HEALTHCARE MATERIALS
卷 11, 期 5, 页码 -出版社
WILEY
DOI: 10.1002/adhm.202101202
关键词
drug delivery; exosomes; extracellular vesicles; liposomes; nucleic acids; siRNA
资金
- European Union [721058]
- VENI Fellowship from the Dutch Research Council (NWO) [VI.Veni.192.174]
- Van Herk Fellowship
- European Research Council (ERC) [725229, 2018B014]
- Dutch Ministry of Economic Affairs, Agriculture and Innovation and the Netherlands CardioVascular Research Initiative (CVON): the Dutch Heart Foundation
- Netherlands Organization for Health Research and Development
- Royal Netherlands Academy of Sciences
- Dutch Heart Foundation [2019T049]
- Dutch Federations of University Medical Centers
EV-liposome hybrid nanoparticles have been investigated as a potential siRNA delivery system, demonstrating their ability to encapsulate siRNA, contain EV-surface markers, and functionally deliver siRNA to different cell types. These hybrids combine the benefits of both synthetic and biological drug delivery systems, showing altered functional behavior compared to liposomes and varying efficacy among recipient cell types.
The therapeutic use of RNA interference is limited by the inability of siRNA molecules to reach their site of action, the cytosol of target cells. Lipid nanoparticles, including liposomes, are commonly employed as siRNA carrier systems to overcome this hurdle, although their widespread use remains limited due to a lack of delivery efficiency. More recently, nature's own carriers of RNA, extracellular vesicles (EVs), are increasingly being considered as alternative siRNA delivery vehicles due to their intrinsic properties. However, they are difficult to load with exogenous cargo. Here, EV-liposome hybrid nanoparticles (hybrids) are prepared and evaluated as an alternative delivery system combining properties of both liposomes and EVs. It is shown that hybrids are spherical particles encapsulating siRNA, contain EV-surface makers, and functionally deliver siRNA to different cell types. The functional behavior of hybrids, in terms of cellular uptake, toxicity, and gene-silencing efficacy, is altered as compared to liposomes and varies among recipient cell types. Moreover, hybrids produced with cardiac progenitor cell (CPC) derived-EVs retain functional properties attributed to CPC-EVs such as activation of endothelial signaling and migration. To conclude, hybrids combine benefits of both synthetic and biological drug delivery systems and might serve as future therapeutic carriers of siRNA.
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