Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System

Sakurai, Yu; Hatakeyama, Hiroto; Akita, Hidetaka; Oishi, Motoi; Nagasaki, Yukio; Futaki, Shiro; Harashima, Hideyoshi

Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System

Sakurai, Yu; Hatakeyama, Hiroto; Akita, Hidetaka et al.

Biological & Pharmaceutical Bulletin, 2009, 32(5), 928-932

Permalink : https://hdl.handle.net/2115/38623

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アクセス権	open access
URI	https://hdl.handle.net/2115/38623
タイトル	Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System
著者	Sakurai, Yu ; Hatakeyama, Hiroto ; Akita, Hidetaka ; Oishi, Motoi ; Nagasaki, Yukio ; Futaki, Shiro ; Harashima, Hideyoshi
著者名 Sakurai, Yu
著者名 Hatakeyama, Hiroto
著者名 Akita, Hidetaka
著者名 Oishi, Motoi
著者名 Nagasaki, Yukio
著者名 Futaki, Shiro
e-Rad_Researcher 00183567 著者名 Harashima, Hideyoshi
言語	英語
キーワード	non-viral delivery system
	stearyl octaarginine
	cancer gene therapy
	multifunctional envelope-type nano device
	pH-sensitive furogenic peptide
発行日	2009-05
出版者	Pharmaceutical Society of Japan
収録物名	Biological & Pharmaceutical Bulletin
巻(号)	32(5)
ページ	928-932
抄録	We recently developed a multifunctional envelope-type nano device (MEND) for efficient nucleic acid delivery. Here, we report on the development of an octaarigine (R8)-modified MEND encapsulating small interfering RNA (siRNA) with a tumor-specific, cleavable, polyethylene glycol (PEG)-lipid (PPD). We first determined the optimal concentration of R8 and pH-sensitive fusogenic peptide (GALA) on the lipid envelope of MEND (R8/GALA-MEND). Then, we examined the combination of optimized R8/GALA-MEND with a PEG-lipid. When a conventional PEG-lipid was used, the R8/GALA-MEND failed to knockdown expression of the target gene. On the other hand, PPD-modified R8/GALA-MEND exhibited efficient silencing activity to the level of the PEG-unmodified R8/GALA-MEND. In addition, we compared a R8/GALA-MEND with a MEND composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) that is a conventional cationic lipid used as a lipoplex component. The knockdown ability of the R8/GALA-MEND was much higher than that of the DOTAP-based MEND at the dose that is commonly employed in in vitro siRNA transfection. These results demonstrate that the R8/GALA-MEND is a promising delivery system for the transfer of siRNA to tumor cells.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	0918-6158
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1248/bpb.32.928