Inhibition of retinal angiogenesis by gold nanoparticles via inducing autophagy
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Corresponding Author:

Jie Shen. Department of Ophthalmology, Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. jshenrenji@163.com

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Supported by the National Natural Science Foundation of China (No.81401063); Shanghai Municipal Planning Commission of Science and Research Fund (No.201740054); Natural Science Foundation of Beijing (No.7153175); the Capital Health Research and Development of Special (No.2018-4-5111); Beijing Nova Program (No.Z16111000490000); Research Foundation for Youth of Second Military Medical University (No.2017QN13); Research Foundation for Youth of Changhai Hospital (No.CH201712; No.CH201820).

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    Abstract:

    AIM: To investigate the effect of gold nanoparticles on retinal angiogenesis in vitro and in vivo, and to reveal the possible mechanism. METHODS: Seed growth method was used to synthesize gold nanoparticles (GNPs). The size, zeta potential, absorption spectrum and morphology of GNPs were identified using Malvern Nano-ZS, multimode reader (BioTek synergy2) and transmission electron microscope. Cell viability was analyzed using cell counting kit-8 method and cell growth was assessed with EdU kit. Transwell chamber was used to investigate cell migration. Tube formation method was used to assess the angiogenic property in vitro. Oxygen induced retinopathy (OIR) model was used to investigate the effect of GNPs on retinal angiogenesis. Confocal microscope and Western blot were used to study the possible mechanism of GNPs inhibited angiogenesis. RESULTS: The GNPs synthesized were uniform and well dispersed. GNPs of 10 μg/mL and 20 μg/mL were able to inhibit human umbilical vein endothelial cells proliferation (50% and 72% separately, P<0.001), migration (54% and 83% separately, P<0.001) and tube formation (52% and 90% separately, P<0.001). Further data showed that GNPs were able to improve the retinopathy in an OIR model. The possible mechanism might be that GNPs were able to induce autophagy significantly (P<0.05). CONCLUSION: The present study suggests that GNPs are able to inhibit retinal neovascularization in vitro and in vivo. GNPs might be a potential nanomedicine for the treatment of retinal angiogenesis.

    Reference
    1 Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011;473(7347):298-307.
    2 Christiaens V, Lijnen HR. Angiogenesis and development of adipose tissue. Mol Cell Endocrinol 2010;318(1-2):2-9.
    3 Dejana E. The role of wnt signaling in physiological and pathological angiogenesis. Circ Res 2010;107(8):943-952.
    4 Chung AS, Ferrara N. Developmental and pathological angiogenesis. Annu Rev Cell Dev Biol 2011;27:563-584.
    5 Rubio RG, Adamis AP. Ocular angiogenesis: vascular endothelial growth factor and other factors. Dev Ophthalmol 2016;55:28-37.
    6 Yang S, Zhao J, Sun X. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review. Drug Des Devel Ther 2016;10:1857-1867.
    7 Li N, Zhao P, Astruc D. Anisotropic gold nanoparticles: synthesis, properties, applications, and toxicity. Angew Chem Int Ed Engl 2014; 53(7):1756-1789.
    8 Daraee H, Eatemadi A, Abbasi E, Fekri Aval S, Kouhi M, Akbarzadeh A. Application of gold nanoparticles in biomedical and drug delivery. Artif Cells Nanomed Biotechnol 2016;44(1):410-422.
    9 Pan Y, Wu Q, Qin L, Cai J, Du B. Gold nanoparticles inhibit VEGF165-induced migration and tube formation of endothelial cells via the Akt pathway. Biomed Res Int 2014;2014:418624.
    10 Pan Y, Ding H, Qin L, Zhao X, Cai J, Du B. Gold nanoparticles induce nanostructural reorganization of VEGFR2 to repress angiogenesis. J Biomed Nanotechnol 2013;9(10):1746-1756.
    11 Kim JH, Kim MH, Jo DH, Yu YS, Lee TG, Kim JH. The inhibition of retinal neovascularization by gold nanoparticles via suppression of VEGFR-2 activation. Biomaterials 2011;32(7):1865-1871.
    12 Ma X, Wu Y, Jin S, Tian Y, Zhang X, Zhao Y, Yu L, Liang XJ. Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment. ACS Nano 2011;5(11):8629-8639.
    13 Ding F, Li Y, Liu J, Liu L, Yu W, Wang Z, Ni H, Liu B, Chen P. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells. Int J Nanomedicine 2014;9:4317-4330.
    14 Jana NR, Gearheart L, Murphy CJ. Seeding growth for size control of 5-40 nm diameter gold nanoparticles. Langmuir 2001; 17(22):6782-6786.
    15 Song H, Wang W, Zhao P, Qi Z, Zhao S. Cuprous oxide nanoparticles inhibit angiogenesis via down regulation of VEGFR2 expression. Nanoscale 2014;6(6):3206-3216.
    16 Shen W, Zhu S, Qin H, Zhong M, Wu J, Zhang R, Song H. EDIL3 knockdown inhibits retinal angiogenesis through the induction of cell cycle arrest in vitro. Mol Med Rep 2017;16(4):4054-4060.
    17 Cao J, Ehling M, März S, Seebach J, Tarbashevich K, Sixta T, Pitulescu ME, Werner AC, Flach B, Montanez E, Raz E, Adams RH, Schnittler H. Polarized actin and VE-cadherin dynamics regulate junctional remodelling and cell migration during sprouting angiogenesis. Nat Commun 2017;8(1):2210.
    18 Rezzola S, Belleri M, Gariano G, Ribatti D, Costagliola C, Semeraro F, Presta M. In vitro and ex vivo retina angiogenesis assays. Angiogenesis 2014;17(3):429-442.
    19 Connor KM, Krah NM, Dennison RJ, Aderman CM, Chen J, Guerin KI, Sapieha P, Stahl A, Willett KL, Smith LE. Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat Protoc 2009; 4(11):1565-1573.
    20 Kimura T, Jia J, Claude-Taupin A, Kumar S, Choi SW, Gu Y, Mudd M, Dupont N, Jiang S, Peters R, Farzam F, Jain A, Lidke KA, Adams CM, Johansen T, Deretic V. Cellular and molecular mechanism for secretory autophagy. Autophagy 2017;13(6):1084-1085.
    21 Du J, Teng RJ, Guan T, Eis A, Kaul S, Konduri GG, Shi Y. Role of autophagy in angiogenesis in aortic endothelial cells. Am J Physiol Cell Physiol 2012;302(2):C383-C391.
    22 Liu J, Fan L, Wang H, Sun G. Autophagy, a double-edged sword in anti-angiogenesis therapy. Med Oncol 2016;33(1):10.
    23 Ramakrishnan S, Nguyen TM, Subramanian IV, Kelekar A. Autophagy and angiogenesis inhibition. Autophagy 2007;3(5):512-515.
    24 Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 2016;12(1):1-222.
    25 Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008;451(7182):1069-1075.
    26 Moscat J, Diaz-Meco MT. p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 2009;137(6):1001-1004.
    27 Li X, Carmeliet P. Targeting angiogenic metabolism in disease. Science 2018;359(6382):1335-1336.
    28 Kroemer G. Autophagy: a druggable process that is deregulated in aging and human disease. J Clin Invest 2015;125(1):1-4.
    29 Duan J, Yu Y, Yu Y, Li Y, Huang P, Zhou X, Peng S, Sun Z. Silica nanoparticles enhance autophagic activity, disturb endothelial cell homeostasis and impair angiogenesis. Part Fibre Toxicol 2014;11(1):50.
    30 Kumar S, Guru S, Pathania A, Kumar A, Bhushan S, Malik F. Autophagy triggered by magnolol derivative negatively regulates angiogenesis. Cell Death Dis 2013;4(10):e889.
    31 Wu Q, Jin R, Feng T, Liu L, Yang L, Tao Y, Anderson JM, Ai H, Li H. Iron oxide nanoparticles and induced autophagy in human monocytes. Int J Nanomedicine 2017;12:3993-4005.
    32 Bjørkøy G, Lamark T, Pankiv S, Øvervatn A, Brech A, Johansen T. Monitoring autophagic degradation of p62/SQSTM1. Meth Enzymol 2009;452:181-197.
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Ni Shen, Rui Zhang, Hao-Rui Zhang,/et al.Inhibition of retinal angiogenesis by gold nanoparticles via inducing autophagy. Int J Ophthalmol, 2018,11(8):1269-1276

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Publication History
  • Received:May 18,2018
  • Revised:June 26,2018
  • Online: August 18,2018