期刊
BIOMATERIALS
卷 32, 期 24, 页码 5733-5742出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2011.04.047
关键词
Liposome; Membrane fusion; Peptide; siRNA delivery; Multi-functional envelop type nano device (MEND)
资金
- New Energy and Industrial Technology Development Organization (NEDO)
- Grants-in-Aid for Scientific Research [10J02352, 22790143, 11J05557] Funding Source: KAKEN
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. (C) 2011 Elsevier Ltd. All rights reserved.
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