A Monotargeting Peptidic Network Antibody Inhibits More Receptors for Anti-Angiogenesis

作者：Kuo Zhang, Hui Zhang, Yong-Hong Gao, Jiaqi Wang, Yuan Li, Hui Cao, Ying Hu, Lei Wang · 发表于：ACS Nano · 年份：2021 · DOI：10.1021/acsnano.1c02194 · 被引用次数：30 · 研究领域：Corneal Surgery and Treatments、Protease and Inhibitor Mechanisms、Proteoglycans and glycosaminoglycans research

The overexpression of growth factors and receptors on neovascular endothelial cells (ECs) and their binding may promote the abnormal growth of new blood vessels, leading to corneal neovascularization (CNV). Normally, monoclonal antibodies may bind and block only one growth factor or receptor, such as bevacizumab binding and blocking vascular endothelial growth factor (VEGF). Herein, we develop a monotargeting peptidic network antibody (pepnetibody) that blocks multiple receptors on the membrane of ECs through forming a fibrous network and ultimately achieves high-efficient treatment of CNV. The pepnetibody could bind to integrin α v β 3 in particulate formulation and in situ fibrillogenesis on ECs, mimicking the process of fibronectin fibrillogenesis on the cell membrane. The in situ formed peptidic network could firmly block integrin and cover other angiogenesis-related receptors, such as VEGF receptor-2 and neuropilin-1, exhibiting competitive efficacy of antiangiogenesis compared with traditional monoclonal antibody bevacizumab with 97.7 times lower dose.