| RRC ID |
37873
|
| Author |
Sakurai Y, Hatakeyama H, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H.
|
| Title |
Efficient short interference RNA delivery to tumor cells using a combination of octaarginine, GALA and tumor-specific, cleavable polyethylene glycol system.
|
| Journal |
Biol Pharm Bull
|
| 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.
|
| Volume |
32(5)
|
| Pages |
928-32
|
| Published |
2009-5-1
|
| DOI |
10.1248/bpb.32.928
|
| PII |
JST.JSTAGE/bpb/32.928
|
| PMID |
19420766
|
| MeSH |
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
|
| IF |
1.863
|
| Times Cited |
35
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
|
| Resource |
| Human and Animal Cells |
HeLa(RCB0007) |
