A dual-modal optical probe for photoacoustic and urine detection of NE activity in atherosclerosis and diabetic complications.

Atherosclerosis is a chronic inflammatory disease of the arterial wall, and neutrophil elastase (NE) has emerged as a key mediator of plaque inflammation and destabilization. In this study, an NE-activatable hemicyanine-based optical probe (NP) was designed and synthesized. Upon specific cleavage by NE, significant activation of absorption, fluorescence, and photoacoustic signals was achieved. In vitro experiments confirmed excellent NE responsiveness, high selectivity, and favorable stability. In vivo studies demonstrated dual hepatic and renal metabolic pathways with good biosafety. The application potential of NP was investigated in three mouse models: healthy controls, atherosclerotic (AS) mice fed a high-fat diet, and AS mice with concurrent diabetes (AS+DM) induced by low-dose streptozotocin. Using photoacoustic imaging, NP sensitively detected increased NE activity within aortic plaques and renal tissues, with the AS+DM group exhibiting the highest signal enhancement. Urine fluorescence analysis further validated the non-invasive diagnostic potential. Collectively, NP represents a promising optical tool for the assessment of plaque inflammation and atherosclerotic disease burden.