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Preparation of arginine-glycine-aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization

Citation

Chang, CY and Wang, MC and Miyagawa, T and Chen, ZY and Lin, FH and Chen, KH and Liu, GS and Tseng, CL, Preparation of arginine-glycine-aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization, International Journal of Nanomedicine, 12 pp. 279-294. ISSN 1178-2013 (2016) [Refereed Article]


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Copyright 2017 Chang et al. Licensed under Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) https://creativecommons.org/licenses/by-nc/3.0/

DOI: doi:10.2147/IJN.S114754

Abstract

Neovascularization (NV) of the cornea can disrupt visual function, causing ocular diseases, including blindness. Therefore, treatment of corneal NV has a high public health impact. Epigalloccatechin-3-gallate (EGCG), presenting antiangiogenesis effects, was chosen as an inhibitor to treat human vascular endothelial cells for corneal NV treatment. An arginine-glycine-aspartic acid (RGD) peptide-hyaluronic acid (HA)-conjugated complex coating on the gelatin/EGCG self-assembly nanoparticles (GEH-RGD NPs) was synthesized for targeting the αvβ3 integrin on human umbilical vein endothelial cells (HUVECs) in this study, and a corneal NV mouse model was used to evaluate the therapeutic effect of this nanomedicine used as eyedrops. HA-RGD conjugation via COOH and amine groups was confirmed by 1H-nuclear magnetic resonance and Fourier-transform infrared spectroscopy. The average diameter of GEH-RGD NPs was 168.8722.5 nm with positive charge (19.72 mV), with an EGCG-loading efficiency up to 95%. Images of GEH-RGD NPs acquired from transmission electron microscopy showed a spherical shape and shell structure of about 200 nm. A slow-release pattern was observed in the nanoformulation at about 30% after 30 hours. Surface plasmon resonance confirmed that GEH-RGD NPs specifically bound to the integrin αvβ3. In vitro cell-viability assay showed that GEH-RGD efficiently inhibited HUVEC proliferation at low EGCG concentrations (20 μg/mL) when compared with EGCG or non-RGD-modified NPs. Furthermore, GEH-RGD NPs significantly inhibited HUVEC migration down to 58%, lasting for 24 hours. In the corneal NV mouse model, fewer and thinner vessels were observed in the alkali-burned cornea after treatment with GEH-RGD NP eyedrops. Overall, this study indicates that GEH-RGD NPs were successfully developed and synthesized as an inhibitor of vascular endothelial cells with specific targeting capacity. Moreover, they can be used in eyedrops to inhibit angiogenesis in corneal NV mice

Item Details

Item Type:Refereed Article
Keywords:RGD peptide, antiangiogenesis, corneal neovascularization, epigallocatechin gallate (EGCG), hyaluronic acid (HA), vascular endothelial cells
Research Division:Technology
Research Group:Medical Biotechnology
Research Field:Gene and Molecular Therapy
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Inherited Diseases (incl. Gene Therapy)
Author:Liu, GS (Dr Guei-Sheung Liu)
ID Code:120655
Year Published:2016
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-08-30
Last Modified:2017-11-13
Downloads:0

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