Delivery of Anti-VEGFA Antibody by Plant-Derived Exosome-like Nanovesicles Alleviates Corneal Angiogenesis and Fibrosis via Topical Ocular Administration.

Background: Pathological angiogenesis and stromal fibrosis after ocular chemical injury are primary drivers of corneal opacification and permanent vision loss. Topical administration of anti-VEGFA antibody is hampered by rapid tear clearance and poor penetration across the corneal epithelial barrier, resulting in insufficient intraocular drug accumulation and suboptimal therapeutic efficacy. Although intraocular injection elevates local drug concentration, this invasive procedure carries risks of complications and is not suitable for long-term repeated treatment. This study constructed red cabbage-derived exosome-like nanovesicles (Rabexo) to load an anti-VEGFA antibody, formulated into PVA/HA hydrogel, aiming to develop a topical sustained-release ocular delivery system for alleviating corneal angiogenic and fibrotic lesions. Methods: Rabexo was isolated and physicochemically characterized. Anti-VEGFA antibody was encapsulated into Rabexo via electroporation to prepare aV-Rabexo, which was further incorporated into commercial PVA/HA hydrogel. Cellular uptake, anti-angiogenic functions were verified in vitro, and therapeutic efficacy was evaluated in a mouse corneal alkali burn model via ophthalmic topical administration. Results: The prepared Rabexo showed uniform size and favorable colloidal stability with 40.3% antibody encapsulation efficiency. aV-Rabexo exhibited stronger in vitro anti-migration, anti-proliferation and anti-tube formation effects than free antibody. In vivo, aV-Rabexo-Gel substantially suppressed corneal neovascular area and length, restored stromal collagen arrangement, and downregulated CD31, VEGFA and α-SMA expression at day 14 post-injury, with statistically significant differences compared with the free antibody gel. Conclusions: This plant-derived nanocarrier hydrogel system realizes synergistic therapeutic effects via nanocarrier delivery, antibody neutralization and prolonged ocular retention. With advantages of easy production and low immunogenicity, it provides a promising non-surgical strategy for treating ocular surface pathological angiogenesis and fibrosis.