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A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/51165

Title: A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo
Authors: Sato, Yusuke Browse this author
Hatakeyama, Hiroto Browse this author →KAKEN DB
Sakurai, Yu Browse this author
Hyodo, Mamoru Browse this author
Akita, Hidetaka Browse this author →KAKEN DB
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Multifunctional envelope-type nano device (MEND)
siRNA delivery
pH-sensitive cationic lipid
Intracellular trafficking
Endosomal escape
Issue Date: 10-Nov-2012
Publisher: Elsevier B.V.
Journal Title: Journal of Controlled Release
Volume: 163
Issue: 3
Start Page: 267
End Page: 276
Publisher DOI: 10.1016/j.jconrel.2012.09.009
PMID: 23000694
Abstract: Modification of liposomal siRNA carriers with polyethylene glycol, i.e., PEGylation, is a generally accepted strategy for achieving in vivo stability and delivery to tumor tissue. However, PEGylation significantly inhibits both cellular uptake and the endosomal escape process of the carriers. In a previous study, we reported on the development of a multifunctional envelope-type nano device (MEND) for siRNA delivery and peptide-based functional devices for overcoming the limitations and succeeded in the efficient delivery of siRNA to tumors. In this study, we synthesized a pH-sensitive cationic lipid, YSK05, to overcome the limitations. The YSK05-MEND had a higher ability for endosomal escape than other MENDs containing conventional cationic lipids. The PEGylated YSK05-MEND induced efficient gene silencing and overcame the limitations followed by optimization of the lipid composition. Furthermore, the intratumoral administration of the YSK05-MEND resulted in a more efficient gene silencing compared with MENDs containing conventional cationic lipids. Collectively, these data confirm that YSK05 facilitates the endosomal escape of the MEND and thereby enhances the efficacy of siRNA delivery into cytosol and gene silencing.
Type: article (author version)
URI: http://hdl.handle.net/2115/51165
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 畠山 浩人

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