Cholesterol-Anchored AND-Logic NIR-II Probe for Triple-Responsive Atherosclerosis Imaging

Early detection of atherosclerosis (AS) is crucial to preventing fatal cardiovascular events, but current imaging still lack sensitivity for early atherosclerotic plaques and microenvironmental risk biomarkers. Here, we developed NKH-CHOL, a cholesterol-anchored near-infrared-II (NIR-II) probe with AND-logic response, to address the critical challenge of early atherosclerosis (AS) detection by synchronously targeting lipid-rich microenvironments and sensing plaque vulnerability biomarkers. This triple-responsive agent leverages cholesterol anchoring for precise localization while concurrently detecting viscosity/polarity shifts from lipid droplet accumulation and hypochlorous acid (HClO) overexpression via myeloperoxidase activity. Featuring a D-π-A structured fluorophore, NKH-CHOL significantly activates only when viscosity/polarity perturbations coexist with HClO, generating NIR-II emission (>1000 nm) with ultralow background. In AS murine models, it achieved high-contrast arterial plaque imaging, representing the first NIR-II molecular tool for simultaneous visualization of lipid metabolism disorders and oxidative stress in atherosclerosis.