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

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 (GOx) 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 GOx 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. A kind of antioxidant and anti-VEGF nanomaterial is prepared using epigallocatechin gallate/gallic acid, Cu(II), and glucose nanozymes. After loading with VEGF-siRNA, the multifunctional nanomaterial is modified with neovascularization targeting cell membrane vesicles. Finally, the constructed bionic nanomedicine is applied in corneal neovascularization, achieving safe, long-lasting, and effective treatment effect.image