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Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA

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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
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)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 畠山 浩人

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