Near-infrared lipid droplet polarity fluorescent probe based on phenothiazine derivative for diagnosis of non-alcoholic fatty liver and tumors.

The polarity of lipid droplets (LDs) is a key indicator of their state and function, playing a crucial regulatory role in diverse biological processes. However, aberrant changes in LDs polarity can disrupt lipid metabolism, resulting in LDs dysfunction and contributing to the development of various diseases, such as obesity, fatty liver and diabetes. Consequently, it is imperative to monitor and track changes in LDs polarity within organisms. Herein, we constructed a D-π-A structure fluorescence probe HAB, using a phenothiazine (PTZ) derivative as electron donor and 4-pyridine-acetonitrile as electron acceptor. This probe accurately monitored the polarity of LDs through the intramolecular charge transfer (ICT) mechanism. Especially, probe HAB exhibited high specificity and sensitivity towards polarity, a significant Stokes shift, and the maximum emission wavelength falling within the near infrared (NIR) region. Within a certain range, both the maximum emission intensity and the maximum emission wavelength of probe HAB exhibited a strong linear correlation with the polarity parameters (Δf). Furthermore, HAB displayed minimal cytotoxicity and enabled wash-free imaging. The probe has high specificity for LDs and could effectively detect the formation and dynamic behavior of LDs. In addition, it successfully monitored changes in LDs polarity under conditions of ferroptosis and anticancer drug therapy. These findings underscore its significant potential for diagnosing non-alcoholic fatty liver disease and tumors, thereby highlighting its value in both disease diagnosis and biological research.