Mitochondrial drug delivery systems for macromolecule and their therapeutic application to mitochondrial diseases.
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.
Yamada
Yuma
Y
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Harashima
Hideyoshi
H
D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods*; D004579:Electron Transport; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008081:Liposomes; D008561:Membrane Fusion; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000628:therapy*; D053758:Nanoparticles; D009696:Nucleic Acids / Q000008:administration & dosage; D011506:Proteins / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D004272:DNA, Mitochondrial; D008081:Liposomes; D009696:Nucleic Acids; D011506:Proteins; D017382:Reactive Oxygen Species