RRC ID 38438
Author Yamada Y, Furukawa R, Yasuzaki Y, Harashima H.
Title Dual function MITO-Porter, a nano carrier integrating both efficient cytoplasmic delivery and mitochondrial macromolecule delivery.
Journal Mol. Ther.
Abstract Mitochondrial dysfunction is associated with a variety of human diseases including inherited mitochondrial diseases, neurodegenerative disorders, diabetes mellitus, and cancer. Effective medical therapies for mitochondrial diseases will ultimately require an optimal drug delivery system, which will likely be achieved through innovations in the nanotechnology of intracellular trafficking. To achieve efficient mitochondrial drug delivery, two independent processes, i.e., "cytoplasmic delivery through the cell membrane" and "mitochondrial delivery through the mitochondrial membrane" are required. In previous studies, we developed an octaarginine (R8) modified nano carrier for efficient cytoplasmic delivery, showing that R8-modified liposomes were internalized into cells efficiently. On the other hand, we also constructed MITO-Porter for the mitochondrial delivery of macromolecules, a liposome-based carrier that delivers cargos to mitochondria via membrane fusion. Here, we report the development of a dual function MITO-Porter (DF-MITO-Porter), based on the concept of integrating both R8-modified liposomes and MITO-Porter. We show that the DF-MITO-Porter effectively delivers exogenous macro-biomolecules into the mitochondrial matrix, and provide a demonstration of its potential use in therapies aimed at mitochondrial DNA.
Volume 19(8)
Pages 1449-56
Published 2011-8
DOI 10.1038/mt.2011.99
PII S1525-0016(16)32514-X
PMID 21694702
PMC PMC3149179
MeSH Biological Transport Cytoplasm / metabolism DNA, Mitochondrial / analysis DNA, Mitochondrial / genetics DNA, Mitochondrial / metabolism* Deoxyribonuclease I / metabolism* Drug Delivery Systems Humans Liposomes / metabolism Macromolecular Substances / metabolism Membrane Fusion Mitochondria / genetics* Mitochondria / metabolism* Mitochondrial Membranes / metabolism Nanostructures* Oligopeptides Protein Transport
IF 7.008
Times Cited 39
Human and Animal Cells