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Experimental Therapeutics, Molecular Targets, and Chemical Biology |
1 Department of Chemistry, Duke University, 2 Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; 3 Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, North Carolina; and 4 Departments of Biomedical Engineering and Chemistry, Metcalf Center for Science and Engineering, Boston University, Boston, Massachusetts
Requests for reprints: David J. Kroll, Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, NC 27709-2194. Phone: 919-485-2605; Fax: 919-541-8868; E-mail: kroll{at}rti.org or Mark W. Grinstaff, Boston University, Boston, MA. E-mail: mgrin{at}bu.edu.
A biocompatible polyester dendrimer composed of the natural metabolites, glycerol and succinic acid, is described for the encapsulation of the antitumor camptothecins, 10-hydroxycamptothecin and 7-butyl-10-aminocamptothecin. The cytotoxicity of the dendrimer-drug complex toward four different human cancer cell lines [human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), nonsmall cell lung carcinoma (NCI-H460), and glioblastoma (SF-268)] is also reported, and low nmol/L IC50 values are measured. Cellular uptake and efflux measurements in MCF-7 cells show an increase of 16-fold for cellular uptake and an increase in drug retention within the cell when using the dendrimer vehicle. (Cancer Res 2006; 66(24): 11913-21)
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