The Preparation And Properties Of Self-assembling Peptide Materials For Inhibiting Angiogenesis

Angiogenesis has been recognized as a target for the tumor therapy.The vascular endothelial growth factor(VEGF)family exerts their biological functions through the interaction with vascular endothelial growth factor receptors(VEGFR).Binding of VEGF to VEGFR leads to proliferation,migration,invasion of endothelial cell and high vascular permeability through downstream signaling pathways.VEGF-VEGFR pathways are essential in tumor angiogenesis,growth and metastasis.Studies on antiangiogenic have been mostly focused on the blockage of VEGF-VEGFR pathways.Peptide-based assembling nanomaterials,as a new intense research subject,has been paid much attention.Many peptides have been developed to inhibit protein-protein interactions.Rationally designed peptides can mimic the binding regions in proteinprotein and antagonize a biological activity of target protein with high specificity.In the present study,we designed a kind of peptide self-assembly materials.It can simulate the biological function of VEGF,bind with VEGFR and decrease the activation of the downstream pathway for inhibiting the migration of endothelial cells and the resulting angiogenesis.The BP-KLVFF-PCAIWF peptide for binding VEGFR was designed with three modules: first,the hydrophobic bis-pyrene(BP)with AIE characteristics for the formation of nanoaggregates and the fluorescence imaging;second,the KLVFF peptide scaffold for the formation of fibers with ?-sheet structures;and the last,the PCAIWF peptide motif that served as a ligand to bind to VEGFR and subsequently induce structural transformation.This peptide first self-assembled into nanoparticles and then transformed into nanofibers,exhibiting enhanced accumulation and retention on the surfaces of endothelial cell.This peptide showed higher efficient inhibition the migration of endothelial cells.On the one hand,the structural transformation from nanoparticles(NPs)into nanofibers(NFs)induced by VEGFR was validated in vitro by multiple techniques.On the other hand,the VEGFR was bound by the ECM-like nanofibrous networks for highly efficient inhibition of the migration of Human Umbilical Vein Endothelial Cells(HUVECs)and the resulting angiogenesis.This material showed excellent potential as an effective VEGFR antibody,which in situ transformed into defensive networks extracellularly for the inhibition of tumor invasion and metastasis.