Yamada Yuma, Harashima Hideyoshi
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Adv Drug Deliv Rev. 2008 Oct-Nov;60(13-14):1439-62. doi: 10.1016/j.addr.2008.04.016. Epub 2008 Jul 4.
Mitochondrial dysfunction has been implicated in a variety of human disorders--the so-called mitochondrial diseases. Therefore, the organelle is a promising therapeutic drug target. In this review, we describe the key role of mitochondria in living cells, a number of mitochondrial drug delivery systems and mitochondria-targeted therapeutic strategies. In particular, we discuss mitochondrial delivery of macromolecules, such as proteins and nucleic acids. The discussion of protein delivery is limited primarily to the mitochondrial import machinery. In the section on mitochondrial gene delivery and therapy, we discuss mitochondrial diseases caused by mutations in mitochondrial DNA, several gene delivery strategies and approaches to mitochondrial gene therapy. This review also summarizes our current efforts regarding liposome-based delivery system including use of a multifunctional envelope-type nano-device (MEND) and mitochondrial liposome-based delivery as anti-cancer therapies. Furthermore, we introduce the novel MITO-Porter--a liposome-based mitochondrial delivery system that functions using a membrane-fusion mechanism.
线粒体功能障碍与多种人类疾病（即所谓的线粒体疾病）有关。因此，该细胞器是一个很有前景的治疗药物靶点。在本综述中，我们描述了线粒体在活细胞中的关键作用、一些线粒体药物递送系统以及线粒体靶向治疗策略。特别是，我们讨论了蛋白质和核酸等大分子的线粒体递送。蛋白质递送的讨论主要限于线粒体导入机制。在关于线粒体基因递送与治疗的部分，我们讨论了由线粒体DNA突变引起的线粒体疾病、几种基因递送策略以及线粒体基因治疗方法。本综述还总结了我们目前在基于脂质体的递送系统方面所做的工作，包括使用多功能包膜型纳米装置（MEND）以及基于线粒体脂质体的递送作为抗癌疗法。此外，我们介绍了新型线粒体转运体——一种基于脂质体的线粒体递送系统，其通过膜融合机制发挥作用。
