Abstract
Here, we report an intrinsic property of gold nanoparticles (nanogold): they can interact selectively with heparin-binding glycoproteins and inhibit their activity. Gold nanoparticles specifically bound vascular permeability factor/vascular endothelial growth factor (VPF/VEGF)-165 and basic fibroblast growth factor, two endothelial cell mitogens and mediators of angiogenesis resulting in inhibition of endothelial/fibroblast cell proliferation in vitro and VEGF-induced permeability as well as angiogenesis in vivo. In contrast, nanogold did not inhibit VEGF-121 or epidermal growth factor, two non-heparin-binding growth factors, mediated cell proliferation. Gold nanoparticles significantly inhibited VEGF receptor-2 phosphorylation, intracellular calcium release, and migration and RhoA activation in vitro. These results report for the first time a novel property of gold nanoparticles to bind heparin-binding proteins and thereby inhibit their subsequent signaling events.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Angiogenesis Inhibitors / pharmacology*
-
Angiogenesis Inhibitors / therapeutic use
-
Animals
-
Calcium / metabolism
-
Cell Line
-
Cell Line, Tumor
-
Cell Movement / drug effects
-
Cell Proliferation / drug effects
-
Endothelial Cells / cytology
-
Endothelial Cells / drug effects
-
Fibroblast Growth Factor 2 / pharmacology
-
Gold / pharmacology*
-
Gold / therapeutic use
-
Humans
-
Intracellular Space / drug effects
-
Intracellular Space / metabolism
-
Male
-
Mice
-
Mice, Inbred C3H
-
Mice, Nude
-
NIH 3T3 Cells
-
Nanotechnology
-
Neoplasm Transplantation
-
Neoplasms, Experimental / blood supply
-
Neoplasms, Experimental / pathology
-
Neoplasms, Experimental / prevention & control
-
Neovascularization, Pathologic / prevention & control
-
Particle Size
-
Phosphorylation / drug effects
-
Umbilical Veins / cytology
-
Vascular Endothelial Growth Factor A / pharmacology
-
Vascular Endothelial Growth Factor Receptor-2 / metabolism
Substances
-
Angiogenesis Inhibitors
-
VEGFA protein, human
-
Vascular Endothelial Growth Factor A
-
Fibroblast Growth Factor 2
-
Gold
-
Vascular Endothelial Growth Factor Receptor-2
-
Calcium