Inhibition of VEGF mediated corneal neovascularization by anti-angiogenic peptide nanofibers
Cubuk, M. O.
Ozmen, M. C.
Guler, M. O.
Tekinay, A. B.
124 - 132
Item Usage Stats
MetadataShow full item record
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.
Site of interests
In vitro study
In vivo study
Scanning transmission electron microscopy
Transmission electron microscopy
Sprague Dawley rat
Published Version (Please cite this version)https://doi.org/10.1016/j.biomaterials.2016.08.045
Showing items related by title, author, creator and subject.
Enhanced immunostimulatory activity of cyclic dinucleotides on mouse cells when complexed with a cell-penetrating peptide or combined with CpG Yildiz, S.; Alpdundar, E.; Gungor, B.; Kahraman, T.; Bayyurt, B.; Gursel, I.; Gursel, M. (Wiley - V C H Verlag GmbH & Co. KGaA, 2015)Recognition of pathogen-derived nucleic acids by immune cells is critical for the activation of protective innate immune responses. Bacterial cyclic dinucleotides (CDNs) are small nucleic acids that are directly recognized ...
Self-assembled peptide amphiphile nanofibers and PEG composite hydrogels as tunable ECM mimetic microenvironment Goktas, M.; Cinar, G.; Orujalipoor, I.; Ide, S.; Tekinay, A. B.; Guler, M. O. (American Chemical Society, 2015)(Figure Presented). Natural extracellular matrix (ECM) consists of complex signals interacting with each other to organize cellular behavior and responses. This sophisticated microenvironment can be mimicked by advanced ...
Cellular internalization of therapeutic oligonucleotides by peptide amphiphile nanofibers and nanospheres Mumcuoglu, D.; S. Ekiz, M.; Gunay, G.; Tekinay, T.; Tekinay, A. B.; Guler, M. O. (American Chemical Society, 2016-04)Oligonucleotides are promising drug candidates due to the exceptionally high specificity they exhibit toward their target DNA and RNA sequences. However, their poor pharmacokinetic and pharmacodynamic properties, in ...