Targeted Delivery of Diphtheria Toxin into VEGFR1/VEGFR2 Overexpressing Cells Induces Anti-angiogenesis Activity

• Published in: Current protein & peptide science Vol. 25; no. 7; p. 567
• Main Authors: Kazemi-Lomedasht, Fatemeh, Taghizadeh-Hesary, Farzad, Faal, Zahra, Behdani, Mahdi
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2024
• Subjects: Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - genetics; Angiogenesis Inhibitors - pharmacology; Cell Movement - drug effects; Cell Survival - drug effects; Diphtheria Toxin - genetics; Diphtheria Toxin - metabolism; Diphtheria Toxin - pharmacology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Gene Expression; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Recombinant Fusion Proteins - pharmacology; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGFR2; diphtheria toxin; VGB3; targeted toxin; VEGFR1; angiogenesis
• ISSN: 1875-5550
• DOI: 10.2174/0113892037292385240222074908

Vascular Endothelial Growth Factor Receptors (VEGFR1 and VEGFR2) are tyrosine kinase receptors expressed on endothelial cells and tumor vessels and play an important role in angiogenesis. In this study, three repeats of VEGFR1 and VEGFR2 binding peptide (VGB3) were genetically fused to the truncated diphtheria toxin (TDT), and its activity was evaluated. The recombinant construct (TDT-triVGB3) was expressed in bacteria cells and purified with nickel affinity chromatography. The binding capacity and affinity of TDT-triVGB3 were evaluated using the enzyme-linked immunosorbent assay. The inhibitory activity of TDT-triVGB3 on viability, migration, and tube formation of human endothelial cells was evaluated using MTT, migration, and tube formation assays. TDT-triVGB3 selectively detected VEGFR1 and VEGFR2 with high affinity in an enzyme- linked immunosorbent assay and significantly inhibited viability, migration, and tube formation of human endothelial cells. The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells.