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ID 57932
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Apriliana Cahya Khayrani Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University ORCID
Mahmud, Hafizah Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University ORCID
Zahra, Maram H. Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Aung Ko Ko Oo Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Oze, Miharu Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Du, Juan Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Alam, Md Jahangir Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Afify, Said M. Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University ORCID
Hagar A. Abu Quora Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Shigehiro, Tsukasa Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University ORCID
Anna Sanchez Calle Division of Molecular and Cellular Medicine, National Cancer Center Research Institute
Okada, Nobuhiro Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Kaken ID researchmap
Seno, Akimasa Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Fujita, Koki Ensuiko Sugar Refining Co., Ltd.
Hamada, Hiroki Faculty of Science, Okayama University of Science
Seno, Yuhki Graduate School of Pharmaceutical Science, Tokushima University
Mandai, Tadakatsu Faculty of Life Science, Kurashiki University of Science and the Arts
Seno, Masaharu Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University ORCID Kaken ID publons researchmap
Abstract
Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15⁻20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies.
Keywords
CD44
glycosylated paclitaxel
liposome
modified paclitaxel
ovarian cancer
specific targeting
Published Date
2019-02-27
Publication Title
International Journal of Molecular Sciences
Volume
volume20
Issue
issue5
Publisher
MDPI
Start Page
1042
ISSN
1422-0067
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2019 by the authors.
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PubMed ID
DOI
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Related Url
isVersionOf https://doi.org/10.3390/ijms20051042
License
http://creativecommons.org/licenses/by/4.0/
Funder Name
Japan Society for the Promotion of Science
助成番号
25242045
26640079
JP18K15243