High-Throughput Screening of Natural Products Alleviating Acute Liver Injury Using a Polarity-Responsive NIR Ratiometric Fluorescent Probe

Acute liver injury (ALI) is a rapidly progressive inflammatory disease lacking precise noninvasive early diagnostic tools, as traditional enzyme-based tests frequently yield false-positive results. Polarity is a crucial physiological indicator, and its abnormal fluctuations are deeply involved in ALI pathogenesis, necessitating accurate in vivo monitoring. We rationally designed BDP-JL, a new near-infrared ratiometric fluorescent probe featuring a D−π–A architecture for highly sensitive polarity detection. It possesses excellent vesicle-targeting capabilities, enabling precise tracking of polarity dynamics within lipid droplets during ALI progression. With exceptional photostability, low cytotoxicity, and ratiometric signal output that effectively eliminates background interference, BDP-JL achieves accurate real-time imaging of polarity variations in live cells, zebrafish, and mice. Furthermore, we successfully utilized it as an optical platform to screen anti-inflammatory natural products. This work provides a robust noninvasive tool for dynamic polarity monitoring, early ALI diagnosis, and high-throughput drug discovery.