Lipid droplet-specific fluorescent biosensor based on triphenylamine derivatives for the diagnosis of non-alcoholic fatty liver disease (NAFLD) at varying stages.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disease caused by excessive accumulation of cellular lipid droplets (LDs). Therefore, the precise monitoring of LDs is of great significance in the development and treatment of NAFLD disease within biomedical research. This study successfully designed and synthesized three near-infrared (NIR), dual-response biosensors DPT-1, DPT-2DPT-3 to precisely monitor the polarity and viscosity of LDs using triphenylamine as electron donors, while coumarone and nitrobenzene units served as electron acceptors. Due to intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) mechanisms, and it can be seen from the comparison with DPT-2 and DPT-3 at the same time, the fluorescence response of the biosensor DPT-1 significantly increased in response to low polarity and high viscosity. Therefore, DPT-1 can selectively target and track the accumulation of LDs in live cells based on their dual-response to viscosity and polarity. Therefore, biosensor DPT-1 was selected for further investigation. Additionally, the biosensor DPT-1 exhibited exceptional selectivity and sensitivity, robust photostability, minimal cytotoxicity, and a significant Stokes shift of 174 nm. Importantly, the biosensor DPT-1 was successfully applied to monitor the accumulation of LDs in live cells and to perform LDs imaging in the liver of mouse models with NAFLD at varying stages. Furthermore, the biosensor DPT-1 exhibited excellent tissue-imaging capabilities, establishing it as a promising tool for the diagnosis of NAFLD at varying stages.