MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion

被引:233
作者
Yamada, Yuma [1 ]
Akita, Hidetaka [1 ]
Kamiya, Hiroyuki [1 ]
Kogure, Kentaro [1 ]
Yamamoto, Takenori [2 ]
Shinohara, Yasuo [2 ]
Yamashita, Kikuji [3 ]
Kobayashi, Hideo [4 ]
Kikuchi, Hiroshi [4 ]
Harashima, Hideyoshi [1 ]
机构
[1] Hokkaido Univ, Fac Pharmaceut Sci, Lab Mol Design Pharmaceut, Kita Ku, Sapporo, Hokkaido 0600812, Japan
[2] Univ Tokushima, Inst Genom Res, Tokushima 7708503, Japan
[3] Univ Tokushima, Inst Hltl Biosci, Tokushima 7708503, Japan
[4] Daiichi Pharmaceut Co Ltd, Tokyo R&D Ctr, Tokyo 1348630, Japan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2008年 / 1778卷 / 02期
关键词
non-viral vector; mitochondria; mitochondrial drug delivery; MITO-Porter; membrane fusion; octaarginine;
D O I
10.1016/j.bbamem.2007.11.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondria are the principal producers of energy in higher cells. Mitochondrial dysfunction is implicated in a variety of human diseases, including cancer and neurodegenerative disorders. Effective medical therapies for such diseases will ultimately require targeted delivery of therapeutic proteins or nucleic acids to the mitochondria, which will be achieved through innovations in the nanotechnology of intracellular trafficking. Here we describe a liposome-based carrier that delivers its macromolecular cargo to the mitochondrial interior via membrane fusion. These liposome particles, which we call MITO-Porters, carry octaarginine surface modifications to stimulate their entry into cells as intact vesicles (via macropinocytosis). We identified lipid compositions for the MITO-Porter which promote both its fusion with the mitochondrial membrane and the release of its cargo to the intra-mitochondrial compartment in living cells. Thus, the MITO-Porter holds promise as an efficacious system for the delivery of both large and small therapeutic molecules into mitochondria. (c) 2007 Elsevier B.V All rights reserved.
引用
收藏
页码:423 / 432
页数:10
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