A stable NIR fluorescent probe for imaging lipid droplets in triple-negative breast cancer

Lipid droplets (LDs) are closely associated various diseases, such as liver diseases and cancers. In the last decade, a mountain of fluorescent probes has been developed for LDs, while the ones bearing near-infrared (NIR) emission, superb specificity, and high stability are still lacking. In this work, we prepare a phenothiazine-derived probe that shows a suitable hydrophobicity with ClogP as 6.25 and a strong emission at 681 nm in the low polarity solvents such as 1,4-dioxane, enabling the NIR imaging of LDs. The probe is verified to showcase high chemostability, superb pH tolerance, and excellent anti-photobleaching capacity. Using the probe, the changes in the polarity, size, and number of LDs can be monitored in living cells under different stimuli. Moreover, a variety of morphological dynamics of LDs is visualized over a period of time, including fusion, fission, transfer of lipid, LD growth, and lipolysis. Utilizing its NIR feature, in vivo tumor imaging is achieved and the therapeutic efficacy of cisplatin is primarily assessed in a triple-negative breast cancer mice model using LDs as the biomarker for the first time. These results suggest that NIR-LD is potential to act as a potent imaging agent for LDs-related diseases.