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ID 52878
FullText URL
Author
Shigehiro, Tsukasa
Kasai, Tomonari Kaken ID researchmap
Murakami, Masaharu
Sekhar, Sreeja C.
Tominaga, Yuki
Okada, Masashi
Kudoh, Takayuki Kaken ID researchmap
Mizutani, Akifumi Kaken ID publons
Murakami, Hiroshi ORCID Kaken ID researchmap
Salomon, David S.
Mikuni, Katsuhiko
Mandai, Tadakatsu
Hamada, Hiroki
Abstract
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.
Published Date
2014-09-29
Publication Title
PLoS ONE
Volume
volume9
Issue
issue9
Publisher
Public Library Science
Start Page
e107976
ISSN
1932-6203
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
File Version
publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1371/journal.pone.0107976
Funder Name
Ministry of Education, Culture, Sports, Science and Technology
助成番号
23650598
25242045
26640079
24510151
24501315