Structurally Engineered Carbonized Polycatechin for Targeting VEGF Signaling and Oxidative Stress in Corneal Neovascularization

Abstract

Corneal neovascularization (CNV) is a condition where abnormal blood vessels grow into the cornea, potentially leading to opacification and blindness. This process is driven by the overexpression of vascular endothelial growth factor (VEGF) and its interaction with the VEGF receptor-2 (VEGFR-2), stimulating angiogenesis. The oxidative stress induced by reactive oxygen species accumulation further promotes the growth of new blood vessels, exacerbating the condition. Therefore, developing a multifaceted treatment capable of inhibiting the VEGF-VEGFR-2 interaction and mitigating oxidative stress is critical. Catechin (Ch), known for its antioxidant, anti-inflammatory, and anti-angiogenic properties, faces limitations in medical use due to its poor bioactivities, low solubility in water, and instability. This research introduced carbonized-polycatechin (c-pCh) to treat CNV, prepared by mild pyrolysis of Ch at 210 degrees C and subsequently undergoing polymerization in an alkaline environment. c-pCh exhibits superior anti-angiogenic capabilities by blocking VEGF-VEGFR-2 interaction and reducing oxidative stress-induced angiogenesis. In a rat model of CNV induced by sutures, c-pCh outperformed monomeric Ch in treatment efficacy. The combined process of carbonization and polymerization presents a promising strategy for developing herbal nanomedicines with enhanced biocompatibility and bioactivity. The outcomes of this study underscore the potent therapeutic potential of c-pCh in CNV management, leveraging its multiple actions.