Efficient short interference RNA delivery to tumor cells using a combination of octaarginine, GALA and tumor-specific, cleavable polyethylene glycol system

Biol Pharm Bull. 2009 May;32(5):928-32. doi: 10.1248/bpb.32.928.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Delivery Systems / methods*
  • Fatty Acids, Monounsaturated / chemistry
  • Gene Silencing / drug effects
  • Gene Transfer Techniques*
  • HeLa Cells
  • Humans
  • Luciferases / genetics
  • Nanoparticles / chemistry
  • Oligopeptides / chemistry*
  • Peptides / chemistry*
  • Polyethylene Glycols / chemistry*
  • Quaternary Ammonium Compounds / chemistry
  • RNA, Small Interfering / administration & dosage*
  • Transfection


  • Fatty Acids, Monounsaturated
  • Oligopeptides
  • Peptides
  • Quaternary Ammonium Compounds
  • RNA, Small Interfering
  • octaarginine
  • GALA peptide
  • Polyethylene Glycols
  • Luciferases
  • 1,2-dioleoyloxy-3-(trimethylammonium)propane