{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T04:04:28Z","timestamp":1768881868186,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,28]],"date-time":"2020-04-28T00:00:00Z","timestamp":1588032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health Research Institute, Taiwan","award":["NHRI-EX105-10334EI"],"award-info":[{"award-number":["NHRI-EX105-10334EI"]}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 106-2628-E-038-001-MY3"],"award-info":[{"award-number":["MOST 106-2628-E-038-001-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health and Medical Research Council of Australia","award":["GNT1185600"],"award-info":[{"award-number":["GNT1185600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Neovascularization (NV) of the cornea disrupts vision which leads to blindness. Investigation of antiangiogenic, slow-release and biocompatible approaches for treating corneal NV is of great importance. We designed an eye drop formulation containing gelatin\/epigallocatechin-3-gallate (EGCG) nanoparticles (NPs) for targeted therapy in corneal NV. Gelatin-EGCG self-assembled NPs with hyaluronic acid (HA) coating on its surface (named GEH) and hyaluronic acid conjugated with arginine-glycine-aspartic acid (RGD) (GEH-RGD) were synthesized. Human umbilical vein endothelial cells (HUVECs) were used to evaluate the antiangiogenic effect of GEH-RGD NPs in vitro. Moreover, a mouse model of chemical corneal cauterization was employed to evaluate the antiangiogenic effects of GEH-RGD NPs in vivo. GEH-RGD NP treatment significantly reduced endothelial cell tube formation and inhibited metalloproteinase (MMP)-2 and MMP-9 activity in HUVECs in vitro. Topical application of GEH-RGD NPs (once daily for a week) significantly attenuated the formation of pathological vessels in the mouse cornea after chemical cauterization. Reduction in both vascular endothelial growth factor (VEGF) and MMP-9 protein in the GEH-RGD NP-treated cauterized corneas was observed. These results confirm the molecular mechanism of the antiangiogenic effect of GEH-RGD NPs in suppressing pathological corneal NV.<\/jats:p>","DOI":"10.3390\/pharmaceutics12050404","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T01:29:15Z","timestamp":1588123755000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Topical Application of Hyaluronic Acid-RGD Peptide-Coated Gelatin\/Epigallocatechin-3 Gallate (EGCG) Nanoparticles Inhibits Corneal Neovascularization via Inhibition of VEGF Production"],"prefix":"10.3390","volume":"12","author":[{"given":"Takuya","family":"Miyagawa","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City 110, Taiwan"},{"name":"B CUBE, Center for Molecular Bioengineering, Technische Universit\u00e4t Dresden, Tatzberg 41, 01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Che-Yi","family":"Chang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ko-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Taipei Veterans General Hospital, Taipei City 112, Taiwan"},{"name":"Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang-Kao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3379-724X","authenticated-orcid":false,"given":"Guei-Sheung","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City 110, Taiwan"},{"name":"Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia"},{"name":"Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC 3002, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9446-4030","authenticated-orcid":false,"given":"Ching-Li","family":"Tseng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City 110, Taiwan"},{"name":"International Ph. D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei City 110, Taiwan"},{"name":"Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei city 110, Taiwan"},{"name":"International Ph. D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei City 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/eye.2011.246","article-title":"Emerging techniques to treat corneal neovascularisation","volume":"26","year":"2012","journal-title":"Eye"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jtos.2012.01.005","article-title":"Corneal neovascularization and the utility of topical VEGF inhibition: Ranibizumab (Lucentis) vs. bevacizumab (Avastin)","volume":"10","author":"Stevenson","year":"2012","journal-title":"Ocul. 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