A polarity-sensitive fluorescent probe for visualizing lipid droplets in ferroptosis, cuproptosis, and autophagy

Dynamics of lipid droplets (LDs) in various pathological processes provides important information about lipid metabolism during theses biological processes, while only a few reports focused on this field. In this work, a benzothiazine-fused coumarin chromophore BCLD with strong fluorescence in low-polarity environment is described. It is confirmed that cyclization-induced rigidification might be a promising approach to enhance the LDs specificity of phenothiazine-based strucutres.The probe is found to enter cells through a clathrin-mediated endocytosis, and is able to monitor LDs variations in living cells, especially during various pathological processes. It is found that obvious increase in polarity of LDs during ferroptosis and cuproptosis was visualized while a dramatic decrease in the number of LDs was recorded during autophagy, indicating different lipid metabolism manners and LD dynamics in these pathological processes. This work supports the potentials of LDs as markers for drug design targeting ferroptosis, cuproptosis, and autophagy.