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针对神经纤毛蛋白-1的特异性纳米抗体的筛选与鉴定及其对血管生成的抑制作用。

Selection and characterization of specific nanobody against neuropilin-1 for inhibition of angiogenesis.

机构信息

Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Mol Immunol. 2020 Dec;128:56-63. doi: 10.1016/j.molimm.2020.10.004. Epub 2020 Oct 15.

Abstract

Neuropilin-1 (NRP-1), non-tyrosine kinase receptor, was initially identified as axonal protein and later recognized as co-receptor for vascular endothelial growth factor (VEGF). Neuropilins (NRPs) are involved in vascular development and tumor angiogenesis. Over the last years, many studies have been accomplished to inhibit angiogenesis. In this study, the nanobody library was panned against immobilized NRP-1 antigen. High affinity and specificity nanobodies were selected through monoclonal ELISA. The selected nanobodies inhibited proliferation and tube formation of HUVEC and MCF-7 cells in vitro and ex vivo. The results highlight potential of anti-NRP1 nanobodies in inhibition of angiogenesis both in vitro and ex vivo and promises development of novel therapeutics against pathologic angiogenesis.

摘要

神经纤毛蛋白-1(NRP-1),一种非酪氨酸激酶受体,最初被鉴定为轴突蛋白,后来被认为是血管内皮生长因子(VEGF)的共受体。神经纤毛蛋白(NRPs)参与血管发育和肿瘤血管生成。在过去的几年中,已经完成了许多研究来抑制血管生成。在这项研究中,纳米抗体文库针对固定化的 NRP-1 抗原进行了筛选。通过单克隆 ELISA 选择了高亲和力和特异性的纳米抗体。体外和离体实验表明,所选纳米抗体抑制了 HUVEC 和 MCF-7 细胞的增殖和管形成。这些结果突出了抗 NRP1 纳米抗体在抑制血管生成方面的潜力,无论是在体外还是在体内,并有望开发针对病理性血管生成的新型治疗方法。

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