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

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)928-932
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume32
Issue number5
DOIs
Publication statusPublished - 2009 May
Externally publishedYes

Keywords

  • Cancer gene therapy
  • Multifunctional envelope-type nano device
  • Non-viral delivery system
  • Ph-sensitive furogenic peptide
  • Stearyl octaarginine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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