Dendrimer-based tumor cell targeting of fibroblast growth factor-1

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:20

Article

Thomas, Thommey P.¹  Shukla, Rameshwer¹  Kotlyar, Alina¹  Kukowska-Latallo, Jola¹  Baker, James R., Jr.¹ 

[1] Univ Michigan, Michigan Nanotechnol Inst Med & Biol Sci, Dept Internal Med, Div Allergy, Ann Arbor, MI 48109 USA

关键词: Dendrimer;    Nanotechnology;    Fibroblast growth factor;    Cancer targeting;    Wound healing;   

DOI  :  10.1016/j.bmcl.2009.11.065

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free