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

Hatakeyama, Hiroto; Murata, Manami; Sato, Yusuke; Takahashi, Mayumi; Minakawa, Noriaki; Matsuda, Akira; Harashima, Hideyoshi

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

Hatakeyama, Hiroto; Murata, Manami; Sato, Yusuke et al.

Journal of controlled release, 2014, 173, 43-50

Permalink : https://hdl.handle.net/2115/57318

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/57318
タイトル	The systemic administration of an anti-miRNA oligonucleotide encapsulated pH-sensitive liposome results in reduced level of hepatic microRNA-122 in mice
著者	Hatakeyama, Hiroto ; Murata, Manami ; Sato, Yusuke ; Takahashi, Mayumi ; Minakawa, Noriaki ; Matsuda, Akira ; Harashima, Hideyoshi
e-Rad_Researcher 70504786 著者名 Hatakeyama, Hiroto
著者名 Murata, Manami
著者名 Sato, Yusuke
著者名 Takahashi, Mayumi
著者名 Minakawa, Noriaki
e-Rad_Researcher 90157313 著者名 Matsuda, Akira
e-Rad_Researcher 00183567 著者名 Harashima, Hideyoshi
言語	英語
キーワード	miRNA
	Antisense oligonucleotide
	Drug delivery system
	Liposomes
	miR-122
発行日	2014-01-10
出版者	Elsevier science bv
収録物名	Journal of controlled release
巻(号)	173
ページ	43-50
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0168-3659
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.jconrel.2013.10.023