title: Gold nanoparticles induce nanostructural reorganization of VEGFR2 to repress angiogenesis.
abstract: The inhibition of the binding between VEGFs and their receptors reduces angiogenesis and retards tumor growth. Owing to the large amount of antibodies required, the antibody-based anti-angiogenic drug remains limited. Gold nanoparticles (AuNPs) displayed excellent biocompatibility, low toxicity and anti-angiogenic effect, but the mechanism of anti-angiogenesis was unknown. Here, the antitumor effects of a well-dispersed AuNPs, specifically regarding its influence on VEGF signaling, were examined mechanistically. The effects of AuNPs on the interaction of VEGF with its receptor, VEGFR2 were observed using near-field scanning optical microscopy/quantum dot (NSOM/QD) imaging. We found AuNPs can reduce VEGF165-induced VEGFR2 and AKT phosphorylation. Furthermore, the antitumor effects of AuNPs were determined using xenograft and ascites model. AuNPs inhibited VEGF165-VEGFR2 interaction and suppressed the formation of nanodomains of VEGFR2 on the HUVEC. As determined by CD34 immunhistochemistry, AuNPs reduced angiogenesis in a liver tumor nude mice model, as observed by a decreased microvascular density in liver tumor sections and reduced the tumor weight and volume. In addition, AuNPs inhibited ascites formation in mice. Taken together, this study provides new insights into nanomaterial-based antitumor drug development.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, P R China. tpanyl@jnu.edu.cn
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Pan
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Zhao
authors.forename: Jiye
authors.initials: J
authors.lastname: Cai
authors.forename: Bin
authors.initials: B
authors.lastname: Du
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D006046:Gold; D040301:Vascular Endothelial Growth Factor Receptor-2