Self‐Cascade API Nanozyme for Synergistic Anti‐Inflammatory, Antioxidant, and Ferroptosis Modulation in the Treatment of Corneal Neovascularization

Corneal neovascularization is a common pathological ocular change that can severely impairs vision, potentially leading to blindness. Although steroids and non-steroidal anti-inflammatory drugs are the primary treatments, their side effects, such as ocular hypertension, eye irritation, and corneal lysis, limit their widespread use. In the present study, an active pharmaceutical ingredient (API) nanozyme (PC-DS NE) is developed through the metal-organic coordination of ferrous sulfate with the anti-inflammatory agent diclofenac sodium and the natural antioxidant proanthocyanidin. PC-DS NE exhibited a spheroid morphology with a particle size of 39.7 ± 5.2 nm, and could achieve the short-term release of diclofenac sodium and sustained release of proanthocyanidin. Notably, the PC-DS NE possessed favorable biocompatibility, self-cascade redox regulation capacity, and significant anti-inflammatory activity. In corneal alkali burn experiments, PC-DS NE effectively inhibited corneal neovascularization by scavenging reactive oxygen species, inhibiting the expression of inflammatory cytokines and pro-angiogenic factors, and down-regulating ferroptosis. These synergistic effects highlighted the potential of PC-DS NE as a promising treatment for ocular inflammatory diseases.