Toward anti-bluing shift: A rationally designed photo-induced electron transfer-based polarity responsive lipid droplets-targeting fluorescent probe for real-time monitoring of drug-induced liver injury.

Drug-induced liver injury (DILI) is a significant public health issue due to its unpredictability and potential severity. DILI primarily manifests as hepatic steatosis or phospholipidosis, accompanied with an elevated lipid droplets (LDs) number. Therefore, developing powerful polarity-responsive probes that target LDs is critical for elucidating the precise function of LDs in DILI. Common solvatochromic polarity-sensitive probes often show a significant blue shift in their emission wavelength as the polarity decreases, with some probes exhibiting a shift of over 100 nm, leading to low accuracy. This wide wavelength coverage required for fluorescence imaging limits their use in multicolor imaging and studies on organelle interactions. In this study, we designed and synthesized a small-molecule environment-sensitive anti-bluing fluorescent probe based on a BODIPY scaffold. This probe was used to investigate dynamic changes in lipid droplets in hepatocytes under a DILI model, thereby providing a foundation for further exploration of the pathophysiological mechanisms underlying DILI-related diseases.