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2015 ; 5
(ä): 10112
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Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids
achieves enhanced cytosolic delivery of exosomes
#MMPMID26011176
Nakase I
; Futaki S
Sci Rep
2015[May]; 5
(ä): 10112
PMID26011176
show ga
Exosomes, which are approximately 100 nm vesicles secreted by cells, have been
studied with respect to cell-to-cell communication, disease diagnosis, and
intracellular delivery. The cellular uptake of exosomes occurs by endocytosis;
however, the cytosolic release efficiency of encapsulated molecules inside cells
is low. To address this issue, here we demonstrate a simple technique for
enhancing the cellular uptake and cytosolic release of exosomes by combining a
pH-sensitive fusogenic peptide for the fusion of endosomal and exosomal membranes
inside cells. This method stimulates the efficient cytosolic release of the
exosomal contents with cationic lipids that act as a "glue" to support cellular
uptake. Using this simple combined technique, the effective cellular uptake and
cytosolic release of an artificially encapsulated dextran macromolecule (70 kDa)
in exosomes are achieved, and a marked improvement in bioactivity is attained
with the artificially encapsulated ribosome-inactivating protein saporin. Our
method will contribute to many biological research fields, including the
assessment of the activities of exosomal contents and the development of
candidate tools enabling intracellular visualisation and cellular regulation for
future therapeutic applications.
|Amino Acid Sequence
[MESH]
|Cations/chemistry
[MESH]
|Cytosol/*metabolism
[MESH]
|Dextrans/chemistry/metabolism
[MESH]
|Endocytosis
[MESH]
|Exosomes/*metabolism
[MESH]
|HeLa Cells
[MESH]
|Humans
[MESH]
|Hydrogen-Ion Concentration
[MESH]
|Lipids/*chemistry
[MESH]
|Microscopy, Confocal
[MESH]
|Molecular Sequence Data
[MESH]
|Peptides/chemistry/*metabolism
[MESH]
|Ribosome Inactivating Proteins, Type 1/chemistry/metabolism
[MESH]