title: Mechanism of anti-angiogenic property of gold nanoparticles: role of nanoparticle size and surface charge.
abstract: Discovering therapeutic inorganic nanoparticles (NPs) is evolving as an important area of research in the emerging field of nanomedicine. Recently, we reported the anti-angiogenic property of gold nanoparticles (GNPs): It inhibits the function of pro-angiogenic heparin-binding growth factors (HB-GFs), such as vascular endothelial growth factor 165 (VEGF165) and basic fibroblast growth factor (bFGF), etc. However, the mechanism through which GNPs imparts such an effect remains to be investigated. Using GNPs of different sizes and surface charges, we demonstrate here that a naked GNP surface is required and core size plays an important role to inhibit the function of HB-GFs and subsequent intracellular signaling events. We also demonstrate that the inhibitory effect of GNPs is due to the change in HB-GFs conformation/configuration (denaturation) by the NPs, whereas the conformations of non-HB-GFs remain unaffected. We believe that this significant study will help structure-based design of therapeutic NPs to inhibit the functions of disease-causing proteins.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Rochelle R
authors.initials: RR
authors.lastname: Arvizo
authors.forename: Subinoy
authors.initials: S
authors.lastname: Rana
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Miranda
authors.forename: Resham
authors.initials: R
authors.lastname: Bhattacharya
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Rotello
authors.forename: Priyabrata
authors.initials: P
authors.lastname: Mukherjee
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors*; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010316:Particle Size; D011487:Protein Conformation; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D006046:Gold