| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-09-27 |
| タイトル |
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タイトル |
Cell-penetrating mechanism of intracellular targeting albumin: Contribution of macropinocytosis induction and endosomal escape |
|
言語 |
en |
| 言語 |
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言語 |
eng |
| キーワード |
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主題 |
Human serum albumin, Cell-penetrating peptide, Macropinocytosis, heparan sulfate proteoglycan, CXCR4, Endosomal escape |
| 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 |
| 著者 |
Ichimizu, Shota
Watanabe, Hiroshi
Maeda, Hitoshi
Hamasaki, Keisuke
Ikegami, Komei
Chuang, Victor Tuan Giam
Kinoshita, Ryo
Nishida, Kento
Shimizu, Taro
Ishima, Yu
Ishida, Tatsuhiro
Seki, Takahiro
Katsuki, Hiroshi
Futaki, Shiroh
Otagiri, Masaki
Maruyama, Toru
|
| 内容記述 |
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内容記述タイプ |
Abstract |
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内容記述 |
We recently developed a cell-penetrating drug carrier composed of albumin (HSA) combined with palmitoyl-cyclic-(D-Arg)12. While it is possible that the palmitoyl-cyclic-(D-Arg)12/HSA enters the cell mainly via macropinocytosis, the mechanism responsible for the induction of macropinocytosis and endosomal escape remain unknown. We report herein that palmitoyl-cyclic-(D-Arg)12/HSA might interact with heparan sulfate proteoglycan and the chemokine receptor CXCR4 followed by multiple activations of the PKC/PI3K/JNK/mTOR signaling pathways to induce macropinocytosis. This result was further confirmed by a co-treatment with 70?kDa dextran, a macropinocytosis marker. Using liposomes that mimic endosomes, the leakage of 5,6-carboxyfluorescein from liposome was observed in the presence of palmitoyl-cyclic-(D-Arg)12/HSA only in the case of the anionic late endosome-like liposomes but not the neutral early endosome-like liposomes. Heparin largely inhibited this leakage, suggesting the importance of electrostatic interactions between palmitoyl-cyclic-(D-Arg)12/HSA and the late-endosomal membrane. Immunofluorescence staining and Western blotting data indicated that the intact HSA could be transferred from endosomes to the cytosol. These collective data suggest that the palmitoyl-cyclic-(D-Arg)12/HSA is internalized via macropinocytosis and intact HSA is released from the late endosomes to the cytoplasm before the endosomes fuse with lysosomes. Palmitoyl-cyclic-(D-Arg)12/HSA not only functions as an intracellular drug delivery carrier but also as an inducer of macropinocytosis. |
| bibliographic_information |
en : Journal of Controlled Release
巻 304,
p. 156-163,
発行年 2019-06-28
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| item_16_source_id_7 |
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収録物識別子 |
0168-3659 |
| 権利 |
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権利情報 |
(C) 2019 Elsevier B.V. All rights reserved. |
| 権利 |
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|
権利情報 |
This manuscript version is made available under the CC-BY-NC-ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| 出版タイプ |
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出版タイプ |
AM |
|
出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 出版者 |
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出版者 |
Elsevier |
| 関連 |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1016/j.jconrel.2019.05.015 |
10.1016_j.jconrel.2019.05.015.pdf (2.3 MB)
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