ID | 52878 |
フルテキストURL | |
著者 |
Shigehiro, Tsukasa
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
Kasai, Tomonari
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
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Murakami, Masaharu
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
Sekhar, Sreeja C.
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
Tominaga, Yuki
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
Okada, Masashi
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
Kudoh, Takayuki
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
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Mizutani, Akifumi
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
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Murakami, Hiroshi
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
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Salomon, David S.
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute
Mikuni, Katsuhiko
Ensuiko Sugar Refining Co., Ltd.
Mandai, Tadakatsu
Faculty of Life Science, Kurashiki University of Science and the Arts
Hamada, Hiroki
Faculty of Science, Okayama University of Science
Seno, Masaharu
Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
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抄録 | Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside.
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発行日 | 2014-09-29
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出版物タイトル |
PLoS ONE
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巻 | 9巻
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号 | 9号
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出版者 | Public Library Science
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開始ページ | e107976
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ISSN | 1932-6203
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1371/journal.pone.0107976
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助成機関名 |
文部科学省
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助成番号 | 23650598
25242045
26640079
24510151
24501315
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