Mitochondrial drug delivery systems for macromolecule and their therapeutic application to mitochondrial diseases

作者：Yamada Yuma; Harashima Hideyoshi^*

来源：Advanced Drug Delivery Reviews, 2008, 60(13-14): 1439-1462.

DOI：10.1016/j.addr.2008.04.016

• Mitochondria
• Mitochondrial drug delivery
• Mitochondrial macromolecule delivery
• MITO-Porter
• Membrane fusion
• Multifunctional envelope-type nano-device (MEND)
• Mitochondrial protein therapy
• Mitochondrial gene therapy
• Mitochondrial protein import machinery
• Mitochondrial DNA

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 macro molecules, 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.

• 出版日期2008-11