Dual Suppression of Oxidative Stress and JAK/STAT3 Signaling Attenuates Inflammation‐Driven Corneal Neovascularization

Corneal neovascularization (CoNV) is a vision-threatening disorder driven by persistent oxidative stress and inflammation, yet effective therapies targeting these interconnected pathological processes remain limited. Here, we identify enhanced signal transducer and activator of transcription 3 (STAT3) phosphorylation and inflammatory signaling in corneal samples from patients with CoNV, as well as reactive oxygen species (ROS) accumulation and macrophage infiltration were observed in an alkali burn-induced mouse model. To address these pathological features, we developed Sta@MSR, a macrophage membrane-cloaked biomimetic nanozyme integrating ruthenium-mediated ROS scavenging with Stattic-mediated STAT3 inhibition. Mechanistically, Sta@MSR attenuated oxidative stress and STAT3-associated inflammatory signaling, thereby suppressing endothelial angiogenic activity and pathological neovascularization. Furthermore, macrophage membrane cloaking enhanced ocular retention and corneal penetration, facilitating topical delivery. Importantly, Sta@MSR markedly reduced pathological neovascularization and inflammatory injury, restored corneal transparency, and exhibited favorable ocular and systemic biocompatibility. Collectively, this work highlights coordinated regulation of oxidative stress and STAT3 signaling as a promising therapeutic strategy for inflammation-driven CoNV.