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

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

doi:10.1248/bpb.32.928

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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

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

Author information

Yu Sakurai
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
CREST, Japan Science and Technology Agency (JST)
Hiroto Hatakeyama
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
CREST, Japan Science and Technology Agency (JST)
Hidetaka Akita
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
CREST, Japan Science and Technology Agency (JST)
Motoi Oishi
Tsukuba Research Center for Interdisciplinary Material Science (TIMS), University of Tsukuba
CREST, Japan Science and Technology Agency (JST)
Yukio Nagasaki
Tsukuba Research Center for Interdisciplinary Material Science (TIMS), University of Tsukuba
CREST, Japan Science and Technology Agency (JST)
Shiro Futaki
Institute for Chemical Research, Kyoto University
Hideyoshi Harashima
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University
CREST, Japan Science and Technology Agency (JST)

Keywords: non-viral delivery system, stearyl octaarginine, cancer gene therapy, multifunctional envelope-type nano device, pH-sensitive furogenic peptide

JOURNAL FREE ACCESS

2009 Volume 32 Issue 5 Pages 928-932

DOI https://doi.org/10.1248/bpb.32.928

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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.

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