Abstract

Ocular neovascular diseases can severely impair vision and increase patients’ economic burden and psychological stress. Currently, anti-VEGF therapy fails to benefit all patients, thus calls for new therapeutic targets and efficient delivery approaches. In this study, we constructed engineered extracellular vesicle—RGD-EV@miR-199a-5p—which are modified with RGD peptide and loaded with miR-199a-5p. This engineered extracellular vesicle offers a dual advantage: the RGD peptide enables precise targeting to neovascular niches, while the combination of miR-199a-5p and the EV platform synergistically inhibits angiogenesis. Experiments in both cultured cells and animals revealed that RGD-EV@miR-199a-5p significantly colocalized with neovascular endothelial cells. Mechanistically, it directly binds to the downstream target gene SNAI1, thereby suppressing protein translation and Wnt/β-catenin signaling. This modulation of the endothelial-mesenchymal transition process ultimately inhibits neovascularization and vascular leakage. Moreover, no significant toxicity was detected at either the cellular or animal level. Collectively, our findings suggest that RGD-EV@miR-199a-5p may represent a promising approach for precisely treating ocular neovascular diseases.