Application of a sulfonic acid-modified NE probe with low-toxicity in a mouse model of pneumonia

Acute lung injury (ALI) induced by pneumonia is a life-threatening disease with high mortality, and neutrophil elastase (NE) overexpression is closely associated with its progression. Herein, a NE-activatable molecular probe SO3-NE was synthesized using hemicyanine dye as the scaffold, modified with sulfonic acid groups to improve water solubility. The probe's performance was systematically evaluated: it exhibited negligible cytotoxicity, high sensitivity (LOD = 0.05 U/L), excellent selectivity for NE, and optimal response at physiological pH 7.4 and 37 °C. In vivo experiments on C57 mice (Healthy, ALI, and SIV-treated groups) showed that SO3-NE specifically imaged NE levels, with ALI group exhibiting significantly higher fluorescence signals than the other two groups. Ex vivo assays and organ HE staining confirmed the probe's reliability and low biotoxicity. This probe provides a promising tool for real-time NE detection during pneumonia progression.