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Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA
Title: | Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA |
Authors: | Sakurai, Yu Browse this author | Hatakeyama, Hiroto Browse this author | Sato, Yusuke Browse this author | Akita, Hidetaka Browse this author | Takayama, Kentaro Browse this author | Kobayashi, Sachiko Browse this author | Futaki, Shiroh Browse this author | Harashima, Hideyoshi Browse this author |
Keywords: | Liposome | Membrane fusion | Peptide | siRNA delivery | Multi-functional envelop type nano device (MEND) |
Issue Date: | Aug-2011 |
Publisher: | Elsevier |
Journal Title: | Biomaterials |
Volume: | 32 |
Issue: | 24 |
Start Page: | 5733 |
End Page: | 5742 |
Publisher DOI: | 10.1016/j.biomaterials.2011.04.047 |
PMID: | 21605898 |
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. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/46877 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 畠山 浩人
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