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ID 114728
Author
Torao, Tasuku Tokushima University
Mimura, Miyuki Tokushima University
Oshima, Yasufumi Tokushima University
Fujikawa, Koki Tokushima University
Hasan, Mahadi JSPS International Research Fellow|Tokushima University
Shimokawa, Tatsuharu Tokushima University
Keywords
Weak current
Cellular uptake
Cytoplasmic delivery
Endosomal leakiness
Ceramide pore
Tubular endocytosis
Content Type
Journal Article
Description
We previously reported that 20 a weak current (WC, 0.3-0.5mA/cm2) applied to cells can induce endocytosis to promote cytoplasmic delivery of hydrophilic macromolecules (MW: < 70,000), such as dextran and siRNA, which leak from WC-induced endosomes into the cytoplasm (Hasan et al., 2016). In this study, we evaluated the characteristics of WC-mediated endocytosis for application of the technology to cytoplasmic delivery of macromolecular medicines. WC induced significantly higher cellular uptake of exogenous DNA fragments compared to untreated cells; the amount increased in a time-dependent manner, indicating that endocytosis was induced after WC. Moreover, following WC treatment of cells in the presence of an antibody (MW: 150,000) with the lysosomotropic agent chloroquine, the antibody was able to bind to its intracellular target. Thus, high molecular weight protein medicines delivered by WC-mediated endocytosis were functional in the cytoplasm. Transmission electron microscopy of cells treated by WC in the presence of gold nanoparticles covered with polyethylene glycol showed that the WC-induced endosomes exhibited an elliptical shape. In the WC-induced endosomes, ceramide, which makes pore structures in the membrane, was localized. Together, these results suggest that WC can induce unique endocytosis and that macromolecular medicines leak from endosomes through a ceramide pore.
Journal Title
International Journal of Pharmaceutics
ISSN
03785173
NCID
AA00680771
AA11530828
Publisher
Elsevier
Volume
576
Start Page
119010
Published Date
2019-12-31
Rights
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
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DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Pharmaceutical Sciences