Item type |
文献 / Documents(1) |
公開日 |
2017-03-07 |
アクセス権 |
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アクセス権 |
open access |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
出版社版DOI |
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関連識別子 |
https://doi.org/10.1016/j.jconrel.2016.02.048 |
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関連名称 |
10.1016/j.jconrel.2016.02.048 |
出版タイプ |
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出版タイプ |
AM |
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出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
タイトル |
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タイトル |
Faint electric treatment-induced rapid and efficient delivery of extraneous hydrophilic molecules into the cytoplasm |
著者 |
Hasan, Mahadi
ニシモト, アキノリ
オオギタ, タカシ
ハマ, ススム
カシダ, ヒロム
アサヌマ, ヒロユキ
小暮, 健太朗
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抄録 |
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内容記述 |
Effective delivery of extraneous molecules into the cytoplasm of the target cells is important for several drug therapies. Previously, we showed effective in vivo transdermal delivery of naked siRNA into skin cells induced by faint electric treatment (ET) iontophoresis, and significant suppression of target mRNA levels (Kigasawa et al., Int. J. Pharm., 2010). This result indicates that electricity promoted the delivery of siRNA into cytoplasm. In the present study, we analyzed the intracellular delivery of naked anti-luciferase siRNA by faint ET, and found that the luciferase activity of cells expressing luciferase was reduced by in vitro ET like in vivo iontophoresis. Cellular uptake of fluorescent-label siRNA was increased by ET, while low temperature exposure, macropinocytosis inhibitor amiloride and caveolae-mediated endocytosis inhibitor filipin significantly prevented siRNA uptake. These results indicate that the cellular uptake mechanism involved endocytosis. In addition, voltage sensitive fluorescent dye DiBAC4 (3) penetration was increased by ET, and the transient receptor potential channel inhibitor SKF96365 reduced siRNA uptake, suggesting that faint ET reduced membrane potentials by changing intracellular ion levels. Moreover, to analyze cytoplasmic delivery, we used in-stem molecular beacon (ISMB), which fluoresces upon binding to target mRNA in the cytoplasm. Surprisingly, cytoplasmic ISMB fluorescence appeared rapidly and homogeneously after ET, indicating that cytoplasmic delivery is markedly enhanced by ET. In conclusion, we demonstrated for the first time that faint ET can enhance cellular uptake and cytoplasmic delivery of extraneous molecules. |
キーワード |
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主題 |
Faint electric treatment |
キーワード |
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主題 |
Cellular uptake |
キーワード |
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主題 |
Cytoplasmic delivery |
書誌情報 |
en : Journal of Controlled Release
巻 228,
p. 20-25,
発行日 2016-03-02
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収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
01683659 |
収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA10458678 |
権利情報 |
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権利情報 |
© 2016 Elsevier B.V. All rights reserved. © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
EID |
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識別子 |
310729 |
言語 |
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言語 |
eng |