A Synergistic Therapy With Antioxidant and Anti‐VEGF: Toward its Safe and Effective Elimination for Corneal Neovascularization

Abstract Corneal neovascularization (CNV) is one of the leading causes of blindness in the world. In clinical practice; however, it remains a challenge to achieve a noninvasive and safe treatment. Herein, a biocompatible shell with excellent antioxidant and antivascularity is prepared by co‐assembly of epigallocatechin gallate/gallic acid and Cu (II). After loading glucose oxidase (GO x ) inside, the shell is modified with dimeric DPA‐Zn for codelivering vascular endothelial growth factor (VEGF) small interfering RNA (VEGF‐siRNA). Meanwhile, the Arg‐Gly‐Asp peptide (RGD) peptide‐engineered cell membranes coating improves angiogenesis‐targeting and is biocompatible for the multifunctional nanomedicine (CEGs/RGD). After eye drops administration, CEGs/RGD targets enrichment in neovascularization and CEGs NPs enter cells. Then, the inner GO x consumes glucose with a decrease in local pH, which in turn leads to the release of EGCE and VEGF‐siRNA. As a result, the nanomedicines significantly reduce angiogenesis and inhibit CNV formation through synergistic effect of antioxidant and antivascular via down‐regulation of cluster of differentiation 31 and VEGF. The nanomedicine represents a safe and efficient CNV treatment through the combined effect of antioxidant/gene, which provides important theoretical and clinical significance.