このエントリーをはてなブックマークに追加
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 Kaken ID researchmap
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 Kaken ID researchmap
Mizutani, Akifumi Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University Kaken ID publons
Murakami, Hiroshi Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University ORCID Kaken ID researchmap
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 ORCID Kaken ID publons researchmap
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.
発行日
2014-09-29
出版物タイトル
PLoS ONE
9巻
9号
出版者
Public Library Science
開始ページ
e107976
ISSN
1932-6203
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
publisher
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1371/journal.pone.0107976
助成機関名
文部科学省
助成番号
23650598
25242045
26640079
24510151
24501315