| PEGylated dendrimers with core functionality for biological applications. | |
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MedLine Citation:
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PMID: 18173227 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The synthesis of a variety of core functionalized PEGylated polyester dendrimers and their in vitro and in vivo properties are described in this report. These water-soluble dendrimers have been designed to carry eight functional groups on their dendritic core for a variety of biological applications such as drug delivery and in vivo imaging as well as eight solubilizing groups. Using a common symmetrical aliphatic ester dendritic core and trifunctional amino acid moieties, a library of dendrimers with phenols, alkyl alcohols, alkynes, ketones, and carboxylic acid functionalities has been synthesized without the need for column chromatography. The amines were PEGylated, leaving the other functionality of the amino acid available for further manipulation such as the attachment of drugs and/or labels. Radiolabeling experiments with the PEGylated dendrimers showed that they had a long circulation half-life in mice, confirming the potential of this class of dendrimers for therapeutic and/or diagnostic applications. A carboxylic acid functionalized dendrimer was elaborated to carry doxorubicin bound via a hydrazone bond. The drug-loaded carrier accumulated more in tumors and less in healthy organs than the clinically used PEGylated liposomal formulation Doxil. The efficient synthesis, high versatility, and favorable biological properties make these PEGylated polyester dendrimers promising structures for therapeutic and/or imaging applications. |
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Authors:
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Steven J Guillaudeu; Megan E Fox; Yarah M Haidar; Edward E Dy; Francis C Szoka; Jean M J Fréchet |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-01-04 |
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: 2008-02-21 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: 461-9 Citation Subset: IM |
Affiliation:
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College of Chemistry, University of California, Berkeley, California 94720-1460, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line, Tumor Dendrimers / chemistry*, pharmacokinetics Magnetic Resonance Spectroscopy Mice Polyethylene Glycols / chemistry*, pharmacokinetics Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Tissue Distribution |
| Grant Support | |
ID/Acronym/Agency:
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EB 002047/EB/NIBIB NIH HHS; GM 65361/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Dendrimers; 0/Polyethylene Glycols |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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