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The systemic administration of an anti-miRNA oligonucleotide encapsulated pH-sensitive liposome results in reduced level of hepatic microRNA-122 in mice

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/57318

Title: The systemic administration of an anti-miRNA oligonucleotide encapsulated pH-sensitive liposome results in reduced level of hepatic microRNA-122 in mice
Authors: Hatakeyama, Hiroto Browse this author →KAKEN DB
Murata, Manami Browse this author
Sato, Yusuke Browse this author
Takahashi, Mayumi Browse this author
Minakawa, Noriaki Browse this author
Matsuda, Akira Browse this author →KAKEN DB
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: miRNA
Antisense oligonucleotide
Drug delivery system
Liposomes
miR-122
Issue Date: 10-Jan-2014
Publisher: Elsevier science bv
Journal Title: Journal of controlled release
Volume: 173
Start Page: 43
End Page: 50
Publisher DOI: 10.1016/j.jconrel.2013.10.023
Abstract: Efficient delivery continues to be a challenge in microRNA (miRNA) therapeutics. We utilized a pH-sensitive multifunctional envelope-type nano device (MEND) containing a pH-sensitive lipid YSK05 (YSK05-MEND) to regulate liver specific miRNA-122 (miR-122). Anti-microRNA oligonucleotides including 2'-OMe and phosphorothioate modifications against miR-122 (AMO122) were encapsulated in the YSK05-MEND. Despite the lower uptake, the YSK05-MEND showed a higher activity in liver cancer cells than Lipofectamine2000 (LFN2k) due to efficient endosomal escape. Cytotoxicity was minimal at 100 nM of AMO122 in YSK05-MEND treated cells, but LFN2k showed toxicity at 50 nM. When mice were administrated with free AMO122, it was eliminated via the kidney due to its molecular weight, and lesser amounts were detected in the liver. Conversely, the YSK05-MEND delivered higher amounts of the AMO122 to the liver. Systemic administration of YSK05-MEND induced the knockdown of miR-122 and an increase in target genes in the liver, and a subsequent reduction in plasma cholesterol at a dose of 1 mg AMO/kg while free AMO122 showed no activity at the same dose. The effect of AMO122 delivered by YSK05-MEND persisted for over 2 weeks. These results suggest that YSK05-MEND is a promising system for delivering AMOs to the liver. (C) 2013 Elsevier B.V. All rights reserved.
Type: article (author version)
URI: http://hdl.handle.net/2115/57318
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: 佐藤 悠介

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