| Synthesis, characterization, antitumor activity of pluronic mimicking copolymer micelles conjugated with doxorubicin via acid-cleavable linkage. | |
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MedLine Citation:
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PMID: 18163537 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pluronic mimicking poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer having multiple hydroxyl groups in the PPO middle segment (core-functionalized Pluronic: CF-PLU) was synthesized for conjugation of doxorubicin (DOX). DOX was conjugated on the multiple hydroxyl groups of CF-PLU via an acid-labile hydrazone linkage (CF-PLU-DOX). In aqueous solution, CF-PLU-DOX copolymers self-assembled to form a core/shell-type micelle structure consisting of a hydrophobic DOX-conjugated PPO core and a hydrophilic PEO shell layer. The conjugated DOX from CF-PLU-DOX micelles was released out more rapidly at pH 5 than pH 7.4, indicating that the hydrazone linkage was cleaved under acidic condition. CF-PLU-DOX micelles exhibited greatly enhanced cytotoxicity for MCF-7 human breast cancer cells compared to naked DOX, while CF-PLU copolymer itself showed extremely low cytotoxicity. Flow cytometry analysis revealed that the extent of cellular uptake for CF-PLU-DOX micelles was greater than free DOX. Confocal image analysis also showed that CF-PLU-DOX micelles had a quite different intracellular distribution profile from free DOX. CF-PLU-DOX micelles were mainly distributed in the cytoplasm, endosomal/lysosomal vesicles, and nucleus, while free DOX was localized mainly within the nucleus, suggesting that CF-PLU-DOX micellar formulation might be advantageously used for overcoming the multidrug resistance (MDR) effect, which gradually develops in many tumor cells during repeated drug administration. |
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Authors:
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Yuhan Lee; Sung Young Park; Hyejung Mok; Tae Gwan Park |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-12-29 |
Journal Detail:
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Title: Bioconjugate chemistry Volume: 19 ISSN: 1043-1802 ISO Abbreviation: Bioconjug. Chem. Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-02-20 Completed Date: 2008-05-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9010319 Medline TA: Bioconjug Chem Country: United States |
Other Details:
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Languages: eng Pagination: 525-31 Citation Subset: IM |
Affiliation:
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Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acids
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chemistry Antineoplastic Agents / chemical synthesis*, pharmacology* Cell Line, Tumor Doxorubicin / chemical synthesis*, pharmacology* Drug Screening Assays, Antitumor Humans Micelles* Microscopy, Electron, Transmission Poloxamer / chemical synthesis*, pharmacology* Scattering, Radiation |
| Chemical | |
Reg. No./Substance:
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0/Acids; 0/Antineoplastic Agents; 0/Micelles; 106392-12-5/Poloxamer; 23214-92-8/Doxorubicin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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