向血管内皮生长因子受体1/血管内皮生长因子受体2过表达细胞靶向输送白喉毒素可诱导抗血管生成活性

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-03-20 DOI:10.2174/0113892037292385240222074908

Fatemeh Kazemi-Lomedasht, Farzad Taghizadeh-Hesary, Zahra Faal, Mahdi Behdani

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引用次数: 0

摘要

背景：血管内皮生长因子受体（VEGFR1 和 VEGFR2）是内皮细胞和肿瘤血管上表达的酪氨酸激酶受体，在血管生成中发挥着重要作用。本研究将 VEGFR1 和 VEGFR2 结合肽（VGB3）的三个重复序列与截短的白喉毒素（TDT）进行基因融合，并对其体外活性进行了评估。方法在细菌细胞中表达重组构建体（TDT-triVGB3），并用镍亲和层析法纯化。用酶联免疫吸附试验评估了 TDT-triVGB3 的结合能力和亲和力。使用 MTT、迁移和管形成试验评估了 TDT-triVGB3 对人内皮细胞活力、迁移和管形成的抑制活性。结果显示在酶联免疫吸附试验中，TDT-triVGB3 能以高亲和力选择性地检测到血管内皮生长因子受体 1 和血管内皮生长因子受体 2，并能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 有可能成为靶向 VEGFR1/ VEGFR2 过度表达癌细胞的新型药物。

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

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 in vitro 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.

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.