期刊
MOLECULAR PHARMACEUTICS
卷 6, 期 2, 页码 457-467出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp800154s
关键词
Ultrasound; microbubbles; intracellular pathway; PEGylated lipoplexes; microjets
资金
- Fund for Scientific Research-Flanders
- Fund for Scientific Research-Flanders (Belgium)
- FWO
- BOF-Ghent
- European Union (via the FP7 Projects Arise and SonoDrugs)
Recently we reported that the transfection of cells by PEGylated lipoplexes becomes significantly better by binding the PEGylated lipoplexes to the surface of microbubbles and applying ultrasound. To further optimize this gene delivery system it is important to understand the working mechanism. This paper elucidates the cellular entry path of these lipoplexes. The results clearly show that the PEGylated lipoplexes, released from the microbubbles upon applying ultrasound, are not taken up by endocytosis, the most common route for nanoparticles to enter cells. Our data demonstrate that, upon implosion of the microbubbles, the PEGylated lipoplexes are released and are most probably able to passively diffuse through the cell membrane pores or become injected in the cytoplasm of the target cells. This is attractive as the in vivo use of PEGylated nanoparticles remains currently limited due to a decreased cellular uptake and inefficient escape of the PEGylated nanoparticles from the endosomes.
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