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Anti‐Flt1 peptide and cyanine‐conjugated gold nanoparticles for the concurrent antiangiogenic and endothelial cell proton treatment
Author(s) -
Seo SeungJun,
Lee SeHee,
Kim KiHong,
Kim JongKi
Publication year - 2019
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.34220
Subject(s) - materials science , biophysics , cytotoxicity , reactive oxygen species , cyanine , peptide , fluorescence , in vitro , biochemistry , chemistry , biology , physics , quantum mechanics
Abstract Anti‐Flt1 peptide of GNQWFI binds to vascular endothelial growth factor receptor 1 (VEGFR1 or Flt1) and prevents binding of VEGF, inhibiting VEGFR1‐mediated endothelial cell migration and tube formation. Bare gold nanoparticle (AuNP) was known to have anti‐angiogenic properties by specific binding with VEGF. In this study, anti‐Flt1 peptide (GGNQWFI) and cyanine were chemically conjugated to AuNPs (Flt1@AuNP‐cyanine 5.5 or Flt1@AuNP‐hydrocyanine 5.5 [HCy5.5]) to enhance antiangiogenic properties with targeting to VEGFR‐1 as well as producing Coulomb nanoradiator therapeutic effect on the retinal endothelial cells. Anti‐Flt1 AuNP complex showed binding with VEGFR‐1 and showed more protein‐induced fluorescence enhancement (PIFE) by various VEGFs compared with bare AuNPs, suggesting enhanced antiangiogenic properties compared to bare AuNP. Nonfluorescent Flt1@AuNP‐HCy5.5 successfully reacted with reactive oxygen species (ROS) produced from Fenton reactions or a proton‐induced Coulomb nanoradiator, enabling quenching‐free oxidant fluorescence ROS imaging in HRMECs under oxidative stress. Flt1@AuNP‐HCy5.5 alone induced 50% greater cytotoxicity for HRMECs compared to bare AuNPs and 80% greater cell death by the Au‐nanoradiator effect. In conclusion, this study describes a new therapeutic anti‐Flt1 gold nanocomplex with enhanced antiangiogenic properties and nanoradiator‐mediated cytotoxicity on retinal endothelial cells. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1272–1283, 2019.