Dendrimer-based tumor cell targeting of fibroblast growth factor-1.
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.
Thomas
Thommey P
TP
Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, Division of Allergy, University of Michigan, 9220 MSRB III, Box 0648, Ann Arbor, MI 48109, United States. thommey@umich.edu
Shukla
Rameshwer
R
Kotlyar
Alina
A
Kukowska-Latallo
Jola
J
Baker
James R
JR
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D016503:Drug Delivery Systems; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011073:Polyamines / Q000737:chemistry; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics
D000970:Antineoplastic Agents; D050091:Dendrimers; D011073:Polyamines; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; D016650:Fluorescein-5-isothiocyanate