Lipid Droplet-Specific Fluorescent Probe for <i>In Vivo</i> Visualization of Polarity in Fatty Liver, Inflammation, and Cancer Models

Elucidating the intrinsic relationship between diseases and lipid droplet (LD) polarity remains a great challenge owing to the lack of the research on multiple disease models. Until now, the visualization of abnormal LD polarity in models of inflammation and clinical cancer patient samples has not been achieved. To meet the urgent challenge, we facilely synthesized a robust LD-specific and polarity-sensitive fluorescent probe (<b>LD</b>-<b>TTP</b>), which consists of a triphenylamine segment as an electron-donor group (D) and a pyridinium as an electron-acceptor moiety (A), forming a typical D-π-A molecular configuration. Owing to the unique intramolecular charge transfer effect, <b>LD-TTP</b> exhibits high sensitivity to polarity change in the linear range from Δ<i>f</i> = 0.258 to 0.312, with over 278-fold fluorescence enhancement. Moreover, we revealed that <b>LD-TTP</b> possessed satisfactory ability for sensitively monitoring LD-polarity changes in living cells. Using <b>LD-TTP</b>, we first demonstrated the detection of LD-polarity changes in fatty liver tissues and inflammatory living mice via confocal laser scanning fluorescence imaging. Surprisingly, the visualization of LD polarity has been achieved not only at the cellular levels and living organs but also in surgical specimens from cancer patients, thus holding great potential in the clinical diagnosis of human cancer. All these features render <b>LD-TTP</b> an effective tool for medical diagnosis of LD polarity-related diseases.