Document Detail

Synthesis, characterization, antitumor activity of pluronic mimicking copolymer micelles conjugated with doxorubicin via acid-cleavable linkage.
MedLine Citation:
PMID:  18163537     Owner:  NLM     Status:  MEDLINE    
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.
Yuhan Lee; Sung Young Park; Hyejung Mok; Tae Gwan Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-29
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  19     ISSN:  1043-1802     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-20     Completed Date:  2008-05-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  525-31     Citation Subset:  IM    
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
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MeSH Terms
Acids / chemistry
Antineoplastic Agents / chemical synthesis*,  pharmacology*
Cell Line, Tumor
Doxorubicin / chemical synthesis*,  pharmacology*
Drug Screening Assays, Antitumor
Microscopy, Electron, Transmission
Poloxamer / chemical synthesis*,  pharmacology*
Scattering, Radiation
Reg. No./Substance:
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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