A novel asymmetric BODIPY-based fluorescent probe for monitoring the polarity of lipid droplets in diabetic models.

Diabetes is a metabolic disease characterized by dysregulated lipid metabolism. As a crucial microenvironmental feature, the polarity of lipid droplets (LDs) is strongly linked to the pathogenesis of diabetes. Thus, developing LDs-specific and polarity-sensitive fluorescent probes is an invaluable tool for the diagnosis of diabetes. Boron dipyrromethene (BODIPY) dyes are promising candidates in the diagnosis of various diseases owing to their excellent optical properties. However, development of fluorescent probes based on BODIPY skeleton for the polarity of LDs is impeded by both the symmetrical structures and inherently small Stokes shifts of BODIPY dyes. Herein, we utilized 2-(isoquinol-1-yl)-pyrrole- boron to construct an asymmetric BODIPY-based fluorescent probe LD-EBA for the polarity of LDs and the diagnosis of diabetes. LD-EBA exhibited excellent chemical stability, a large Stokes shift (∼153 nm), and high fluorescence quantum yield (81.4%). In addition, LD-EBA can target LDs and detect their polarity with high selectivity. Remarkably, LD-EBA successfully utilized fluorescence to visualize the polarity of lipid droplets in both diabetic models and LPS-induced inflammation models. In addition, in vivo imaging revealed the association of the polarity of LDs with diabetes, and simultaneously captured the hepatic and renal injury induced by diabetes. Featuring a novel asymmetric design, LD-EBA advances the expands the structural development of BODIPY-derived fluorescent probes. The present findings provide a robust optical method for early-stage diabetes diagnosis through the detection of LD polarity as a potential marker.