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

Abstract

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.

Semaphorin3A Exacerbates Cardiac Microvascular Rarefaction in Pressure Overload‐Induced Heart Disease

“…NRP1 is a cell-surface receptor [33,34] that is intimately involved in the development of the cardiovascular system, [34] pathogenic angiogenesis, [35,36] and organogenesis outside the nervous system. [33,37] Previous studies have reported that NRP-1 is predominantly expressed in the heart by endothelial cells, fibroblasts, and smooth muscle cells.…”

In situ stimulus-responsive self-assembled nanomaterials for drug delivery and disease treatment

“…(C) Molecular structure of LAFH and a cartoon of LAFH nanoparticles. 104 Copyright 2021, the American Chemical Society. (D) The structure of self-assembly peptide and TDS transformation.…”

“…4C and 5A). 104 NF networks on tumor cells can significantly block tumor cell-induced platelet agglutination in vitro and prevent platelet adhesion around circulating tumor cells (CTCs) in vivo, limiting the pro-metastatic effect of platelets and preventing early metastasis. 105 Based on the verification of the peptide sequence targeting the integrin a V b 3 receptor, the targeted receptor can be replaced by a cluster of differentiation (CD), such as the CD3 protein, to obtain an enhanced self-assembly effect that promotes receptor oligomerization and T cell activation to exert immune effects.…”

“…5 (A) A schematic illustration of contact of LAFH NPs and integrin a V b 3 to form LAFH NFs. 104 Copyright 2021, the American Chemical Society. (B) Nanofibrous barriers formed by TDS suppress metastasis of renal cancer by dual inhibition of vascular endothelium and CSCs.…”

Precise Control of Self‐assembly in vivo Based on Polymer‐Peptide Conjugates†

“…fibrous network and achieves high‐efficient treatment of CNV. [ 88 ] The peptide (lauric acid‐FFVLK‐HSDVHK (LAFH)) can trap α v β 3 and form a fibrous network through self‐assembly of the KLVFF sequence on the membrane of neovascular endothelial cells. The fiber nanostructure also can cover other angiogenesis‐related receptors, such as VEGFR2 and NRP‐1, showing great potential for antiangiogenesis.…”