title: Antiangiogenic properties of gold nanoparticles.
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.
authors.affiliation: Department of Biochemistry, Mayo Clinic Cancer Center, Rochester, Minnesota 55905, USA.
authors.forename: Priyabrata
authors.initials: P
authors.lastname: Mukherjee
authors.forename: Resham
authors.initials: R
authors.lastname: Bhattacharya
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Sujit
authors.initials: S
authors.lastname: Basu
authors.forename: Janice A
authors.initials: JA
authors.lastname: Nagy
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Debabrata
authors.initials: D
authors.lastname: Mukhopadhyay
authors.forename: Shay
authors.initials: S
authors.lastname: Soker
mesh_terms: 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
chemical_list: 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