A sulfur-substituted hemicyanine-based activatable probe for photoacoustic visualization of neutrophil elastase in liver I/R injury

Hepatic ischemia-reperfusion (I/R) injury is a major clinical complication, and the precise monitoring of key inflammatory mediators like neutrophil elastase (NE) in vivo remains a significant challenge. To address this, we developed HDS-NE, a highly specific and activatable molecular probe based on a sulfur-substituted hemicyanine scaffold, engineered for the simultaneous detection of NE via fluorescence and photoacoustic imaging modalities. The probe demonstrated exceptional sensitivity and selectivity toward NE, enabling the real-time visualization of elevated NE activity in a murine model of hepatic I/R injury. Both in vivo and ex vivo imaging results confirmed a markedly enhanced signal in injured livers compared to controls, which was further validated by serum assays and histology. Crucially, this study represents the successful achievement of non-invasive, in vivo imaging of NE activity during hepatic I/R processes, offering a powerful tool for diagnosing and studying inflammatory liver diseases.