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      Inhibition of VEGF mediated corneal neovascularization by anti-angiogenic peptide nanofibers

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      Author(s)
      Senturk, B.
      Cubuk, M. O.
      Ozmen, M. C.
      Aydin B.
      Güler, Mustafa O.
      Tekinay, A. B.
      Date
      2016-11
      Source Title
      Biomaterials
      Print ISSN
      0142-9612
      Publisher
      Elsevier
      Volume
      107
      Pages
      124 - 132
      Language
      English
      Type
      Article
      Item Usage Stats
      231
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      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-angiogenesis
      Corneal 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/11693/36871
      Published Version (Please cite this version)
      https://doi.org/10.1016/j.biomaterials.2016.08.045
      Collections
      • Institute of Materials Science and Nanotechnology (UNAM) 2258
      • Nanotechnology Research Center (NANOTAM) 1179
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