Multi-enzyme nanozyme targeting redox-senescence-angiogenesis axis ameliorates pathological angiogenesis in retinopathy models

) through a Fenton-independent mechanism, enabling efficient and sustained ROS elimination without generating harmful hydroxyl radicals. This redox reprogramming capacity effectively alleviated oxidative stress-triggered endothelial cell senescence and suppressed abnormal angiogenesis, primarily through modulation of the MAPK signaling pathway, thereby promoting vascular normalization and restoring retinal microenvironmental stability. In an oxygen-induced retinopathy (OIR) mouse model, PBzyme treatment elicited a pronounced reduction in both the avascular area (approximately 3-fold) and pathological neovascular tufts (approximately 19-fold), as evidenced by retinal whole-mount analyses. Furthermore, in a diabetic retinopathy (DR) mouse model, PBzyme administration significantly mitigated retinal vascular leakage by approximately 3-fold. Collectively, PBzyme represents a novel, biocompatible nanozyme platform that uniquely targets the redox-senescence-angiogenesis axis. Its potent multi-enzyme mimetic activity and distinct non-Fenton mechanism offer a promising and transformative therapeutic strategy for retinal neovascular diseases.