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Cancer Research 66, 11913, December 15, 2006. doi: 10.1158/0008-5472.CAN-06-2066
© 2006 American Association for Cancer Research
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Experimental Therapeutics, Molecular Targets, and Chemical Biology

Dendrimer-Encapsulated Camptothecins: Increased Solubility, Cellular Uptake, and Cellular Retention Affords Enhanced Anticancer Activity In vitro

Meredith T. Morgan1, Yuka Nakanishi3, David J. Kroll3, Aaron P. Griset4, Michael A. Carnahan2, Michel Wathier4, Nicholas H. Oberlies3, Govindarajan Manikumar3, Mansukh C. Wani3 and Mark W. Grinstaff4

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), non–small 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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[Abstract] [Full Text] [PDF]


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Copyright © 2006 by the American Association for Cancer Research.