Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA

Sakurai, Yu; Hatakeyama, Hiroto; Sato, Yusuke; Akita, Hidetaka; Takayama, Kentaro; Kobayashi, Sachiko; Futaki, Shiroh; Harashima, Hideyoshi

Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA

Sakurai, Yu; Hatakeyama, Hiroto; Sato, Yusuke et al.

Biomaterials, 2011, 32(24), 5733-5742

Permalink : https://hdl.handle.net/2115/46877

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アクセス権	open access
URI	https://hdl.handle.net/2115/46877
タイトル	Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA
著者	Sakurai, Yu ; Hatakeyama, Hiroto ; Sato, Yusuke ; Akita, Hidetaka ; Takayama, Kentaro ; Kobayashi, Sachiko ; Futaki, Shiroh ; Harashima, Hideyoshi
著者名 Sakurai, Yu
著者名 Hatakeyama, Hiroto
著者名 Sato, Yusuke
著者名 Akita, Hidetaka
著者名 Takayama, Kentaro
著者名 Kobayashi, Sachiko
著者名 Futaki, Shiroh
著者名 Harashima, Hideyoshi
言語	英語
キーワード	Liposome
	Membrane fusion
	Peptide
	siRNA delivery
	Multi-functional envelop type nano device (MEND)
発行日	2011-08
出版者	Elsevier
収録物名	Biomaterials
巻(号)	32(24)
ページ	5733-5742
抄録	An siRNA that specifically silences the expression of mRNA is a potential therapeutic agent for dealing with many diseases including cancer. However, the poor cellular uptake and bioavailability of siRNA remains a major obstacle to clinical development. For efficient delivery to tumor tissue, the pharmacokinetics and intracellular trafficking of siRNA must be rigorously controlled. To address this issue, we developed a liposomal siRNA carrier, a multi-functional nano device (MEND). We describe herein an approach for systemic siRNA delivery to tumors by combining the MEND system with shGALA, a fusogenic peptide. In cultured cell experiments, shGALA-modification enhanced the endosomal escape of siRNA encapsulated in a polyethylene glycol modified MEND (PEG-MEND), resulting in an 82% knockdown of the target gene. In vivo systemic administration clarified that the shGALA-modified MEND (shGALA-MEND) showed 58% gene silencing in tumor tissues at a dose of 4 mg of siRNA/kg body weight. In addition, a significant inhibition of tumor growth was observed only for the shGALA-MEND and no somatic or hepatic toxicity was observed. Given the above data, this peptide-modified delivery system, a shGALA-MEND has great potential for the systemic delivery of therapeutic siRNA aimed at cancer therapy.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0142-9612
関連情報	PMID 21605898
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.biomaterials.2011.04.047