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

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Title: Efficient Short Interference RNA Delivery to Tumor Cells Using a Combination of Octaarginine, GALA and Tumor-Specific, Cleavable Polyethylene Glycol System
Authors: Sakurai, Yu Browse this author
Hatakeyama, Hiroto Browse this author
Akita, Hidetaka Browse this author
Oishi, Motoi Browse this author
Nagasaki, Yukio Browse this author
Futaki, Shiro Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: non-viral delivery system
stearyl octaarginine
cancer gene therapy
multifunctional envelope-type nano device
pH-sensitive furogenic peptide
Issue Date: May-2009
Publisher: Pharmaceutical Society of Japan
Journal Title: Biological & Pharmaceutical Bulletin
Volume: 32
Issue: 5
Start Page: 928
End Page: 932
Publisher DOI: 10.1248/bpb.32.928
Abstract: 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.
Type: article
URI: http://hdl.handle.net/2115/38623
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: 原島 秀吉

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