Development of a multifunctional envelope-type nano device and its application to nanomedicine

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• 作者：Yusuke Sato ; Takashi Nakamura ; Yuma Yamada ; Hideyoshi Harashima ; ^{harasima@pharm.hokudai.ac.jp}
• 关键词：Nanomedicines ; MEND ; siRNA ; Cancer therapy ; Hepatitis ; Mitochondria
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 December 2016
• 年：2016
• 卷：244
• 期：part_PB
• 页码：194-204
• 全文大小：1365 K
• 卷排序：244

文摘

Successful nanomedicines should be based on sound drug delivery systems (DDS) the permit intracellular trafficking as well as the biodistribution of cargos to be controlled. We have been developing new types of DDS that are multifunctional envelope-type nano devices referred to as MENDs. First, we will focus the in vivo delivery of siRNA to hepatocytes using a YSK-MEND which is composed of pH-responsive cationic lipids. The YSK-MEND is capable of inducing efficient silencing activity in hepatocytes and can be used to cure mice that are infected with hepatitis C or B. The YSK-MEND can also be applied to cancer immunotherapy through the activation of immune cells by delivering different compounds such as cyclic-di-GMP, siRNA or alpha-galactosylceramide as a lipid antigen. The findings indicate that, as predicted, these compounds, when encapsulated in the YSK-MEND, can be delivered to the site of action and induced immune activation through different mechanisms. Finally, a MITO-Porter, a membrane fusion-based delivery system to mitochondria, is introduced as an organelle targeting DDS and a new strategy for cancer therapy is proposed by delivering gentamicin to mitochondria of cancer cells. These new technologies are expected to extend the therapeutic area of Nanomedicine by increasing the power of DDS, especially from the view point of controlled intracellular trafficking.