Inhibition of VEGF mediated corneal neovascularization by anti-angiogenic peptide nanofibers
Date
2016-11Source Title
Biomaterials
Print ISSN
0142-9612
Publisher
Elsevier
Volume
107
Pages
124 - 132
Language
English
Type
ArticleItem Usage Stats
231
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views
430
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Abstract
Atypical angiogenesis is one of the major symptoms of severe eye diseases, including corneal neovascularization, and the complex nature of abnormal vascularization requires targeted methods with high biocompatibility. The targeting of VEGF is the most common approach for preventing angiogenesis, and the LPPR peptide sequence is known to strongly inhibit VEGF activity by binding to the VEGF receptor neuropilin-1. Here, the LPPR epitope is presented on a peptide amphiphile nanofiber system to benefit from multivalency and increase the anti-angiogenic function of the epitope. Peptide amphiphile nanofibers are especially useful for ocular delivery applications due to their ability to remain on the site of interest for extended periods of time, facilitating the long-term presentation of bioactive sequences. Consequently, the LPPR sequence was integrated into a self-assembled peptide amphiphile network to increase its efficiency in the prevention of neovascularization. Anti-angiogenic effects of the peptide nanofibers were investigated by using both in vitro and in vivo models. LPPR-PA nanofibers inhibited endothelial cell proliferation, tube formation, and migration to a greater extent than the soluble LPPR peptide in vitro. In addition, the LPPR-PA nanofiber system led to the prevention of vascular maturation and the regression of angiogenesis in a suture-induced corneal angiogenesis model. These results show that the anti-angiogenic activity exhibited by LPPR peptide nanofibers may be utilized as a promising approach for the treatment of corneal angiogenesis.
Keywords
Anti-angiogenesisCorneal neovascularization
Neuropilin-1
Peptide amphiphiles
Amphiphiles
Biocompatibility
Cell proliferation
Complex networks
Endothelial cells
Epitopes
Nanofibers
Polypeptides
Angiogenesis
Anti-angiogenic activity
Neo-vascularization
Neuropilin-1
Peptide amphiphiles
Peptide sequences
Self-assembled peptides
Site of interests
Peptides
Animal model
Animal tissue
Antiangiogenic activity
In vitro study
In vivo study
Priority journal
Rat
Scanning transmission electron microscopy
Suture
Transmission electron microscopy
Animal
Chemistry
Cornea neovascularization
Metabolism
Pathology
Sprague Dawley rat
Treatment outcome
Angiogenesis Inhibitors
Permalink
http://hdl.handle.net/11693/36871Published Version (Please cite this version)
https://doi.org/10.1016/j.biomaterials.2016.08.045Collections
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