Document Detail


Biodegradable block copolymer-doxorubicin conjugates via different linkages: preparation, characterization, and in vitro evaluation.
MedLine Citation:
PMID:  20604578     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Doxorubicin (Dox) was conjugated onto a biodegradable block copolymer methoxy-poly(ethylene glycol)-block-poly(lactide-co-2,2-dihydroxymethylpropylene carbonate (mPEG-b-P(LA-co-DHP)) via a carbamate linkage and an acid-labile hydrazone linkage, respectively. Mutifunctional mixed micelles consisting of Dox-containing copolymer mPEG-b-P(LA-co-DHP/Dox) and folic acid-containing copolymer mPEG-b-P(LA-co-DHP/FA) were successfully prepared by coassembling the two component copolymers. The mixed micelles had well-defined core shell structure and their diameters were in the range of 70-100 nm. Both Dox-conjugates (via carbamate or hydrazone linkage) showed pH-dependent release behavior, and the micelles with hydrazone linkage showed more pH-sensitivity compared to those with carbamate linkage. The in vitro cell uptake experiment by CLSM and flow cytometry showed preferential internalization of FA-containing micelles by human ovarian cancer cell line SKOV-3 than that without FA. Flow cytometric analysis was conducted to reveal the enhanced cell apoptosis caused by the FA-containing micelles. These results suggested that these micelles containing both chemotherapeutic and targeting ligand could be a promising nanocarrier for targeting the drugs to cancer cells and releasing the drug molecules inside the cancer cells.
Authors:
Xiuli Hu; Shi Liu; Yubin Huang; Xuesi Chen; Xiabin Jing
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biomacromolecules     Volume:  11     ISSN:  1526-4602     ISO Abbreviation:  Biomacromolecules     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-09     Completed Date:  2010-12-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2094-102     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemistry,  metabolism*,  pharmacology
Apoptosis / drug effects
Cell Line, Tumor
Chromatography, Gel
Doxorubicin / chemistry,  metabolism*,  pharmacology
Drug Screening Assays, Antitumor
Flow Cytometry
Humans
Magnetic Resonance Spectroscopy
Microscopy, Electron, Transmission
Polymers / chemistry,  metabolism*,  pharmacology
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Polymers; 23214-92-8/Doxorubicin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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