An “AND” Logic Gated Near-Infrared Fluorescent Probe Simultaneously Sensing Superoxide Anion and Viscosity Enables Early Atherosclerosis Monitoring

Early stages of atherosclerosis (AS) involve macrophage lipid uptake and oxidative stress, creating a dynamic microenvironment that drives plaque initiation. Monitoring the complex chemical and physical changes in the lesion is essential for understanding disease and developing early diagnostic strategies. However, real-time and specific monitoring of key molecular events remain challenging. Here, we constructed a near-infrared (NIR) dual-locked fluorescent probe, PLAQ-SCAN (Plaque Localization and Qualification via Superoxide and Viscosity Co-activated Analysis). The fluorescence turn on depends on the coexistence of both stimuli, precisely matching the "dual dysregulation" microenvironment of early AS and effectively avoiding false positive signals induced by a single stimulus. The results demonstrated that PLAQ-SCAN exhibits strong fluorescence only in the presence of both signals and successfully monitors the dysregulation of superoxide anion (O2•-) and viscosity during macrophage foam formation. Notably, PLAQ-SCAN was able to track the AS progression of aortic plaques and detect serum signals changes as week 8, preceding conventional histopathological evidence. In summary, PLAQ-SCAN provides a powerful platform to real-time monitor O2•- and viscosity during pathogenesis, enabling early AS monitoring and synergistic mechanistic exploration.