title: Ultrastrong trapping of VEGF by graphene oxide: Anti-angiogenesis application.
abstract: Angiogenesis is the process of formation of new blood vessels, which is essential to human biology, and also plays a crucial role in several pathologies such as tumor growth and metastasis, exudative age-related macular degeneration, and ischemia. Vascular endothelial growth factor (VEGF), in particular, VEGF-A165is the most important pro-angiogenic factor for angiogenesis. Thus, blocking the interaction between VEGFs and their receptors is considered an effective anti-angiogenic strategy. We demonstrate for that first time that bovine serum albumin-capped graphene oxide (BSA-GO) exhibits high stability in physiological saline solution and possesses ultrastrong binding affinity towards VEGF-A165[dissociation constant (Kd) ∼3 × 10-12M], which is at least five orders of magnitude stronger than that of high-abundant plasma proteins such as human serum albumin, fibrinogen, transferrin, and immunoglobulin G. Due to the surprising binding specificity of BSA-GO for VEGF-A165in complex plasma fluid, we have also studied the anti-angiogenic effects in vitro and in vivo. Results show that BSA-GO not only effectively inhibits the proliferation, migration and tube formation of human umbilical vein endothelial cells, but also strongly disturbs the physiological process of angiogenesis in chick chorioallantoic membrane and blocks VEGF-A165-induced blood vessel formation in rabbit corneal neovascularization. Our findings indicate that GO nanomaterials can potentially act as therapeutic anti-angiogenic agents via ultrastrong VEGF adsorption and its activity suppression.
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Pei-Xin
authors.initials: PX
authors.lastname: Lai
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Chung-Wein
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Shih-Chun
authors.initials: SC
authors.lastname: Wei
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan.
authors.forename: Tzu-Yu
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan.
authors.forename: Hong-Jyuan
authors.initials: HJ
authors.lastname: Jian
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Irving Po-Jung
authors.initials: IP
authors.lastname: Lai
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Ju-Yi
authors.initials: JY
authors.lastname: Mao
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Pang-Hung
authors.initials: PH
authors.lastname: Hsu
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Han-Jia
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Wen-Shyong
authors.initials: WS
authors.lastname: Tzou
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Shiow-Yi
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Université de Montréal, Montréal, Québec, H3C 3J7, Canada.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Harroun
authors.affiliation: Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan; Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan; Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan. Electronic address: jylai@mail.cgu.edu.tw.
authors.forename: Jui-Yang
authors.initials: JY
authors.lastname: Lai
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan; Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. Electronic address: huanging@ntou.edu.tw.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Huang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D016510:Corneal Neovascularization / Q000473:pathology; D005123:Eye / Q000187:drug effects; D006108:Graphite / Q000737:chemistry* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D049329:Nanostructures; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010087:Oxides / Q000737:chemistry*; D011485:Protein Binding; D011817:Rabbits; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013499:Surface Properties; D013816:Thermodynamics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D010087:Oxides; D042461:Vascular Endothelial Growth Factor A; D012710:Serum Albumin, Bovine; D006108:Graphite
keywords: Anti-angiogenesis; Blood vessel; Corneal neovascularization; Graphene oxide; Serum albumin; Vascular endothelial growth factor