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),...

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Bibliographic Details
Published in:Biomaterials 2016-12, Vol.109, p.12-22
Main Authors: Lai, Pei-Xin, Chen, Chung-Wein, Wei, Shih-Chun, Lin, Tzu-Yu, Jian, Hong-Jyuan, Lai, Irving Po-Jung, Mao, Ju-Yi, Hsu, Pang-Hung, Lin, Han-Jia, Tzou, Wen-Shyong, Chen, Shiow-Yi, Harroun, Scott G, Lai, Jui-Yang, Huang, Chih-Ching
Format: Article
Language:English
Subjects:
Advanced Basic Science
Angiogenesis Inhibitors - pharmacology
Animals
Anti-angiogenesis
Binding
Blood vessel
Blood vessels
Cattle
Cell Movement - drug effects
Cell Proliferation - drug effects
Chemical compounds
Chick Embryo
Chorioallantoic Membrane - blood supply
Chorioallantoic Membrane - drug effects
Corneal neovascularization
Corneal Neovascularization - pathology
Dentistry
Eye - drug effects
Formations
Graphene
Graphene oxide
Graphite - chemistry
Graphite - pharmacology
Human Umbilical Vein Endothelial Cells - cytology
Human Umbilical Vein Endothelial Cells - drug effects
Humans
Nanostructures
Neovascularization, Physiologic - drug effects
Oxides
Oxides - chemistry
Protein Binding
Rabbits
Serum albumin
Serum Albumin, Bovine - chemistry
Strategy
Surface Properties
Thermodynamics
Trapping
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
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Summary: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-A165 is 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 × 10−12  M], 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-A165 in 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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2016.09.005