| RRC ID |
38422
|
| 著者 |
Sakurai Y, Hatakeyama H, Sato Y, Akita H, Takayama K, Kobayashi S, Futaki S, Harashima H.
|
| タイトル |
Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA.
|
| ジャーナル |
Biomaterials
|
| Abstract |
An siRNA that specifically silences the expression of mRNA is a potential therapeutic agent for dealing with many diseases including cancer. However, the poor cellular uptake and bioavailability of siRNA remains a major obstacle to clinical development. For efficient delivery to tumor tissue, the pharmacokinetics and intracellular trafficking of siRNA must be rigorously controlled. To address this issue, we developed a liposomal siRNA carrier, a multi-functional nano device (MEND). We describe herein an approach for systemic siRNA delivery to tumors by combining the MEND system with shGALA, a fusogenic peptide. In cultured cell experiments, shGALA-modification enhanced the endosomal escape of siRNA encapsulated in a polyethylene glycol modified MEND (PEG-MEND), resulting in an 82% knockdown of the target gene. In vivo systemic administration clarified that the shGALA-modified MEND (shGALA-MEND) showed 58% gene silencing in tumor tissues at a dose of 4 mg of siRNA/kg body weight. In addition, a significant inhibition of tumor growth was observed only for the shGALA-MEND and no somatic or hepatic toxicity was observed. Given the above data, this peptide-modified delivery system, a shGALA-MEND has great potential for the systemic delivery of therapeutic siRNA aimed at cancer therapy.
|
| 巻・号 |
32(24)
|
| ページ |
5733-42
|
| 公開日 |
2011-8-1
|
| DOI |
10.1016/j.biomaterials.2011.04.047
|
| PII |
S0142-9612(11)00469-8
|
| PMID |
21605898
|
| MeSH |
Animals
Cell Line, Tumor
Endosomes / metabolism*
Gene Silencing / physiology
HeLa Cells
Humans
Liposomes / chemistry*
Male
Mice
Mice, Inbred ICR
Mice, Nude
Peptides / metabolism*
Peptides / pharmacology*
Polyethylene Glycols / chemistry
RNA, Small Interfering / chemistry*
|
| IF |
10.317
|
| 引用数 |
86
|
|
WOS 分野
|
ENGINEERING, BIOMEDICAL
MATERIALS SCIENCE, BIOMATERIALS
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007)
HT1080(RCB1956) |
