https://scholars.lib.ntu.edu.tw/handle/123456789/463906
Title: | Preparation of arginine–glycine–aspartic acid-modified biopolymeric nanoparticles containing epigalloccatechin-3-gallate for targeting vascular endothelial cells to inhibit corneal neovascularization | Authors: | Chang, C.-Y. Wang, M.-C. Miyagawa, T. Chen, Z.-Y. Lin, F.-H. Chen, K.-H. Liu, G.-S. Tseng, C.-L. Lin, Feng-Huei |
Keywords: | Antiangiogenesis; Corneal neovascularization; Epigallocatechin gallate (EGCG); Hyaluronic acid (HA); RGD peptide; Vascular endothelial cells | Issue Date: | 2017 | Journal Volume: | 12 | Start page/Pages: | 279-294 | Source: | International Journal of Nanomedicine | 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 168.87±22.5 nm with positive charge (19.7±2 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. ? 2017 Chang et al. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/463906 | DOI: | 10.2147/IJN.S114754 | SDG/Keyword: | arginylglycylaspartic acid; biopolymer; epigallocatechin gallate; eye drops; nanoparticle; vitronectin receptor; angiogenesis inhibitor; arginyl-glycyl-aspartic acid; catechin; epigallocatechin gallate; eye drops; hyaluronic acid; nanoparticle; oligopeptide; vitronectin receptor; animal experiment; animal model; Article; cell proliferation; cell shape; cell viability; controlled study; cornea neovascularization; drug delivery system; drug efficacy; drug screening; drug structure; drug targeting; human; human cell; infrared spectroscopy; mouse; nanoencapsulation; nanopharmaceutics; nonhuman; particle size; proton nuclear magnetic resonance; surface plasmon resonance; transmission electron microscopy; vascular endothelial cell; zeta potential; analogs and derivatives; animal; Burns, Chemical; C57BL mouse; cell survival; chemistry; Corneal Neovascularization; disease model; drug effects; Eye Burns; metabolism; molecularly targeted therapy; pathology; procedures; umbilical vein endothelial cell; Angiogenesis Inhibitors; Animals; Burns, Chemical; Catechin; Cell Survival; Corneal Neovascularization; Disease Models, Animal; Eye Burns; Human Umbilical Vein Endothelial Cells; Humans; Hyaluronic Acid; Integrin alphaVbeta3; Mice, Inbred C57BL; Molecular Targeted Therapy; Nanoparticles; Oligopeptides; Ophthalmic Solutions |
Appears in Collections: | 醫學工程學研究所 |
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