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 |
Design and tuning of a cell-penetrating albumin derivative as a versatile nanovehicle for intracellular drug delivery |
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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, Drug binding, Albumin fusion technology, Palmitate high affinity binding site |
資源タイプ |
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資源タイプ |
journal article |
著者 |
Ichimizu, Shota
Watanabe, Hiroshi
Maeda, Hitoshi
Hamasaki, Keisuke
Nakamura, Yuka
Chuang, Victor Tuan Giam
Kinoshita, Ryo
Nishida, Kento
Tanaka, Ryota
Enoki, Yuki
Ishima, Yu
Kuniyasu, Akihiko
Kobashigawa, Yoshihiro
Morioka, Hiroshi
Futaki, Shiro
Otagiri, Masaki
Maruyama, Toru
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内容記述 |
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内容記述 |
Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA. Among the CPPs evaluated, a cyclic polypeptide composed of D-dodecaarginines, palmitoyl-cyclic-(D-Arg)12 was the most effective for facilitating the cellular uptake of HSA by HeLa cells. Such a superior cell-penetrating capability is primarily mediated by macropinocytosis. The effect of the CPP on pharmacological activity was examined using three drugs loaded in HSA via three different methods: a) an HSA-paclitaxel complex, b) an HSA-doxorubicin covalent conjugate and c) an HSA-thioredoxin fusion protein. The results showed that cell-penetrating efficiency was increased with a corresponding and significant enhancement in pharmacological activity. In conclusion, palmitoyl-cyclic-(D-Arg)12/HSA is a versatile cell-penetrating drug delivery system with great potential for use as a nano-carrier for a wide diversity of pharmaceutical applications. |
bibliographic_information |
en : Journal of Controlled Release
巻 277,
p. 23-24,
発行年 2018-05-10
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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) 2018 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 |
出版者 |
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出版者 |
Elsevier |
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言語 |
en |
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.2018.02.037 |