Antiangiogenic properties of gold nanoparticles.
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.
Mukherjee
Priyabrata
P
Department of Biochemistry, Mayo Clinic Cancer Center, Rochester, Minnesota 55905, USA.
Bhattacharya
Resham
R
Wang
Ping
P
Wang
Ling
L
Basu
Sujit
S
Nagy
Janice A
JA
Atala
Anthony
A
Mukhopadhyay
Debabrata
D
Soker
Shay
S
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006046:Gold / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D036103:Nanotechnology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010316:Particle Size; D010766:Phosphorylation / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D006046:Gold; D040301:Vascular Endothelial Growth Factor Receptor-2; D002118:Calcium