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

被引:36
作者
Thomas, Thommey P. [1 ]
Shukla, Rameshwer [1 ]
Kotlyar, Alina [1 ]
Kukowska-Latallo, Jola [1 ]
Baker, James R., Jr. [1 ]
机构
[1] Univ Michigan, Michigan Nanotechnol Inst Med & Biol Sci, Dept Internal Med, Div Allergy, Ann Arbor, MI 48109 USA
基金
美国国家卫生研究院;
关键词
Dendrimer; Nanotechnology; Fibroblast growth factor; Cancer targeting; Wound healing; NUCLEAR TRANSLOCATION; FACTOR RECEPTORS; DELIVERY; ANGIOGENESIS; MECHANISMS; EXPRESSION; CANCER; FGF-1;
D O I
10.1016/j.bmcl.2009.11.065
中图分类号
R914 [药物化学];
学科分类号
100705 [微生物与生化药学];
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.
引用
收藏
页码:700 / 703
页数:4
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