In Situ Imaging of Extracellular Vesicles and Non-Alcoholic Fatty Liver Disease with a Near-Infrared Fluorescent Viscosity Probe.

Extracellular vesicles (EVs) have significant value in disease diagnosis. Non-alcoholic fatty liver disease (NAFLD) has become a global health issue, and real-time monitoring of NAFLD is crucial to prevent its further deterioration. However, due to the lack of effective probes, in situ detection of EVs in living systems is still challenging, which hinders the application of EVs in the diagnosis of NAFLD and other diseases. Herein, we report a novel fluorescent probe, ND-N, capable of selectively imaging EVs, achieving the in situ detection of NAFLD for the first time using EVs as biomarkers. ND-N has a good water solubility and is sensitive to viscosity. As the viscosity increases, its near-infrared fluorescence is significantly enhanced. More importantly, ND-N can achieve selective wash-free imaging of EVs in living cells and can also target and image the liver through intravenous injection. By the establishment of a NAFLD mouse model, ND-N was successfully applied for in situ imaging of changes of EVs in the liver during the NAFLD process. The results showed that the number and viscosity of EVs in the liver of NAFLD mice significantly increased, indicating that EVs can serve as biomarkers for NAFLD fluorescence imaging, and ND-N, as an excellent probe for EVs, shows great potential in NAFLD diagnosis.