Non-invasive visualization of hepatic neutrophil elastase activity via a sulfonate-modified molecular probe in...

Neutrophil elastase (NE) is a key protease implicated in the pathogenesis of inflammatory metabolic diseases, yet tools for its non-invasive detection in deep tissues are limited. This study presents the development and validation of S-NEP, a sulfonate-modified hemicyanine-based molecular probe, for the specific sensing and photoacoustic imaging of NE activity. S-NEP demonstrated exceptional selectivity for NE over other biological analytes, a sensitive turn-on photoacoustic and fluorescent response upon activation, and high biocompatibility. In vivo photoacoustic imaging in a diet-induced murine model of obesity revealed a significant elevation of hepatic NE activity, which correlated positively with disease progression from early to late stages. This finding was corroborated by ex vivo immunohistochemistry, histology, and serological fluorescence assays. The successful application of S-NEP for quantifying NE activity directly in serum samples further underscores its considerable potential for translational diagnostic applications in metabolic diseases.