A Sulfonic Acid-Functionalized NIR Probe for Neutrophil Elastase Detection in Cardiovascular Diseases

This study presents WK-NE, an innovative near-infrared (NIR) fluorescent probe engineered for highly sensitive and selective detection of neutrophil elastase (NE), a key inflammatory protease implicated in cardiovascular diseases. Distinguished by its unique structural design, WK-NE incorporates a sulfonic acid group into its hemicyanine scaffold, significantly enhancing water solubility and eliminating the need for post-synthetic modifications—a critical advancement over conventional hydrophobic probes. The probe operates through an intramolecular charge transfer (ICT) mechanism, exhibiting a 5-fold fluorescence enhancement at 735 nm upon NE activation with exceptional specificity (R 2 = 0.9949, linear range 0–2.5 U/L) and minimal interference from biological analytes (<5% signal variation). WK-NE demonstrates superior performance in physiological conditions (optimal pH 7.4, 37°C) and successfully tracks NE dynamics in living macrophages, mouse models, and clinical samples. Notably, it reveals progressive NE elevation in serum and cerebrospinal fluid of cardiovascular patients, correlating with disease severity, representing a transformative tool for cardiovascular research and clinical translation.