MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion.
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.
Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Yuma
Y
Yamada
Hidetaka
H
Akita
Hiroyuki
H
Kamiya
Kentaro
K
Kogure
Takenori
T
Yamamoto
Yasuo
Y
Shinohara
Kikuji
K
Yamashita
Hideo
H
Kobayashi
Hiroshi
H
Kikuchi
Hideyoshi
H
Harashima
D000818:Animals; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D008297:Male; D008561:Membrane Fusion; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D008081:Liposomes