Lu Lu, Chen Hongyuan, Hao Dake, Zhang Xinke, Wang Fengshan
Key Laboratory of Chemical Biology (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Department of General Surgery, Shandong University Affiliated Shandong Provincial Hospital, Jinan 250021, China.
Asian J Pharm Sci. 2019 Nov;14(6):595-608. doi: 10.1016/j.ajps.2019.04.004. Epub 2019 May 25.
Vascular endothelial growth factor receptor 2 (VEGFR-2) and neuropilin-1 (NRP-1) are two prominent antiangiogenic targets. They are highly expressed on vascular endothelial cells and some tumor cells. Therefore, targeting VEGFR-2 and NRP-1 may be a potential antiangiogenic and antitumor strategy. A7R, a peptide with sequence of Ala-Thr-Trp-Leu-Pro-Pro-Arg that was found by phage display of peptide libraries, can preferentially target VEGFR-2 and NRP-1 and destroy the binding between vascular endothelial growth factor 165 (VEGF165) and VEGFR-2 or NRP-1. This peptide is a new potent inhibitor of tumor angiogenesis and a targeting ligand for cancer therapy. This review describes the discovery, function and mechanism of the action of A7R, and further introduces the applications of A7R in antitumor angiogenic treatments, tumor angiogenesis imaging and targeted drug delivery systems. In this review, strategies to deliver different drugs by A7R-modified liposomes and nanoparticles are highlighted. A7R, a new dual targeting ligand of VEGFR-2 and NRP-1, is expected to have efficient therapeutic or targeting roles in tumor drug delivery.
血管内皮生长因子受体2（VEGFR - 2）和神经纤毛蛋白-1（NRP - 1）是两个重要的抗血管生成靶点。它们在血管内皮细胞和一些肿瘤细胞上高表达。因此，靶向VEGFR - 2和NRP - 1可能是一种潜在的抗血管生成和抗肿瘤策略。A7R是一种通过噬菌体展示肽库发现的序列为Ala - Thr - Trp - Leu - Pro - Pro - Arg的肽，它可以优先靶向VEGFR - 2和NRP - 1，并破坏血管内皮生长因子165（VEGF165）与VEGFR - 2或NRP - 1之间的结合。这种肽是一种新型强效肿瘤血管生成抑制剂和癌症治疗的靶向配体。本文综述了A7R的发现、功能及作用机制，并进一步介绍了A7R在抗肿瘤血管生成治疗、肿瘤血管生成成像及靶向给药系统中的应用。本文重点介绍了通过A7R修饰的脂质体和纳米颗粒递送不同药物的策略。A7R作为一种新型的VEGFR - 2和NRP - 1双靶向配体，有望在肿瘤药物递送中发挥高效的治疗或靶向作用。
