2024-03-28T12:34:14Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/468772022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALASakurai, YuHatakeyama, HirotoSato, YusukeAkita, HidetakaTakayama, KentaroKobayashi, SachikoFutaki, ShirohHarashima, HideyoshiLiposomeMembrane fusionPeptidesiRNA deliveryMulti-functional envelop type nano device (MEND)499An 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.ElsevierJournal Articleapplication/pdfhttp://hdl.handle.net/2115/46877https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/46877/1/Bio32-24_5733-5742.pdf0142-9612Biomaterials3224573357422011-08enginfo:pmid/21605898info:doi/10.1016/j.biomaterials.2011.04.047author