Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 20, Issue 2, Pages 700-703Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.11.065
Keywords
Dendrimer; Nanotechnology; Fibroblast growth factor; Cancer targeting; Wound healing
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Funding
- National Cancer Institute, National Institutes of Health [R33 CA112141, 1 R21 RR021893]
- National Institute of Biomedical Imaging and Bio-Engineering, National Institutes of Health [RO1 EB005028]
- National Institute of Diabetes & Digestive & Kidney Diseases [NIH5P60 DK20572]
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Fibroblast Growth Factor Receptor (FGFR) is overexpressed in a wide variety of tumors, and therefore is an attractive target for drug delivery. Recombinant FGF-1 was purified and attached to a fifth-generation (G5) polyamidoamine dendrimer. The specific binding and internalization of this conjugate labeled with FITC was demonstrated by flow cytometry as well as by confocal microscopic analysis in cell lines expressing FGFR. The binding and uptake of FGF-conjugated dendrimers was completely blocked by excess nonconjugated FGF-1. Confocal microscopic analysis showed cytosolic as well as nuclear localization. Multivalent G5-FGF nanoparticles may serve as a platform for cytosolic as well as nuclear drug delivery in tumor cells, and as an FGF delivery agent for angiogenesis and wound healing. Our study shows for the first time the applicability of a dendrimer nanodevice for tumor cell targeting through FGFR. (C) 2009 Elsevier Ltd. All rights reserved.
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