論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa(RCB0007) HT1080(RCB1956) |