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Mitochondrial drug delivery and mitochondrial disease therapy--an approach to liposome-based delivery targeted to mitochondria.

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Title: Mitochondrial drug delivery and mitochondrial disease therapy--an approach to liposome-based delivery targeted to mitochondria.
Authors: Yamada, Yuma Browse this author
Akita, Hidetaka Browse this author
Kogure, Kentaro Browse this author
Kamiya, Hiroyuki Browse this author
Harashima, Hideyoshi Browse this author
Keywords: Mitochondrial drug delivery
Mitochondrial protein therapy
Mitochondrial gene therapy
Transferrin and GALA system
multifunctional envelope-type nano device (MEND)
Regulation of intramitochondrial trafficking
Issue Date: Feb-2007
Publisher: Elsevier
Journal Title: Mitochondrion
Volume: 7
Issue: 1-2
Start Page: 63
End Page: 71
Publisher DOI: 10.1016/j.mito.2006.12.003
PMID: 17296332
Abstract: Recent progress in genetics and molecular biology has provided useful information regarding the molecular mechanisms associated with the mitochondrial diseases. Genetic approaches were initiated in the late 1980s to clarify the gene responsible for various mitochondrial diseases, and information concerning genetic mutations is currently used in the diagnosis of mitochondrial diseases. Moreover, it was also revealed that mitochondria play a central role in apoptosis, or programmed cell death, which is closely related to the loss of physiological functions of tissues. Therefore, drug therapies targeted to the mitochondria would be highly desirable. In spite of the huge amount of mechanism-based studies of mitochondrial diseases, effective therapies have not yet been established mainly because of the lack of an adequate delivery system. To date, numerous investigators have attempted to establish a mitochondrial drug delivery system. However, many problems remain to be overcome before a clinical application can be achieved. To fulfill a drug delivery targeted to mitochondria, we first need to establish a method to encapsulate various drugs, proteins, peptides, and genes into a drug carrier depending on their physical characteristics. Second, we need to target it to a specific cell. Finally, multi-processes of intracellular trafficking should be sophisticatedly regulated so as to release a drug carrier from the endosome to the cytosol, and thereafter to deliver to the mitochondria. In this review, we describe the current state of the development of mitochondrial drug delivery systems, and discuss the advantage and disadvantage of each system. Our current efforts to develop an efficient method for the packaging of macromolecules and regulating intracellular trafficking are also summarized. Furthermore, novel concept of "Regulation of intramitochondrial trafficking" is proposed herein as a future challenge to the development of a mitochondrial drug delivery system.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山田 勇磨

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