靶向递送白喉毒素至 VEGFR1/VEGFR2 过表达细胞诱导抗血管生成活性。
Targeted Delivery of Diphtheria Toxin into VEGFR1/VEGFR2 Overexpressing Cells Induces Anti-angiogenesis Activity.
机构信息
Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
出版信息
Curr Protein Pept Sci. 2024;25(7):567-576. doi: 10.2174/0113892037292385240222074908.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells.
背景
血管内皮生长因子受体（VEGFR1 和 VEGFR2）是表达在内皮细胞和肿瘤血管上的酪氨酸激酶受体，在血管生成中发挥重要作用。在这项研究中，将 VEGFR1 和 VEGFR2 结合肽（VGB3）的三个重复序列基因融合到截短的白喉毒素（TDT）上，并评估其活性。
方法
重组构建体（TDT-triVGB3）在细菌细胞中表达，并通过镍亲和层析进行纯化。使用酶联免疫吸附试验评估 TDT-triVGB3 的结合能力和亲和力。使用 MTT、迁移和管形成测定法评估 TDT-triVGB3 对人内皮细胞活力、迁移和管形成的抑制活性。
结果
TDT-triVGB3 在酶联免疫吸附试验中选择性地以高亲和力检测 VEGFR1 和 VEGFR2，并显著抑制人内皮细胞的活力、迁移和管形成。
结论
开发的 TDT-triVGB3 可能是一种针对 VEGFR1/VEGFR2 过表达癌细胞的新型靶向药物。
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