Bispecific Peptide Binds to VEGFR2 and Integrin αvβ3, Forming an Artificial Extracellular Matrix for Anti‐Ocular Neoangiogenesis

Abstract Ocular neovascularization (NV) leads to vision loss in various pathological conditions. Current therapies primarily inhibit vascular endothelial growth factor (VEGF) signaling; however, targeting additional pathways may improve outcomes. A bispecific peptide (BsPt) is developed that targets VEGFR2 and integrin αvβ3 to treat retinal neovascularization (RNV) and choroidal neovascularization (CNV) more effectively. BsPt binds to both receptors on endothelial cells (ECs) and forms nanofibrous networks on their surfaces, resulting in potent NV inhibition. In vitro, BsPt suppressed retinal EC migration and tube formation. Intravitreal BsPt injection outperformed aflibercept in mouse models of oxygen‐induced retinopathy (OIR) and laser‐induced CNV. RNA sequencing revealed that BsPt‐induced nanofibers upregulated extracellular matrix (ECM) and cell adhesion genes, which may contribute to anti‐angiogenesis and anti‐leakage effects. In summary, BsPt targeting VEGFR2 and integrin αvβ3 demonstrates enhanced therapeutic potential for RNV and CNV.