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Playing central roles in energy homeostasis and lipid metabolism, lipid droplets (LDs) also contribute to cellular protein trafficking and maturation and are associated with several human diseases. A dozen of fluorescent probes are known so far, and most of them sense either the less polar or the more viscous environment of LDs compared to that of cytosol. Described herein is a rational approach to the deep-red emitting LD probe that senses both the nonpolar and highly viscous environment of LDs. This dual sensing probe is chemically stable, not responding to typical biothiols and reactive oxygen species, and also photochemically stable suitable for long-term monitoring of LDs. The probe is proven to be efficient for the detection of LDs, as demonstrated by several in cellulo imaging experiments for HeLa cells under starvation and under an excess level of oleic acid, and also for 3T3-L1 cells that differentiate into an adipocyte-like phenotype. Image 1 • The probe TCFAN targets both the nonpolar and highly viscose environment that lipid droplets provide. • Emission in the deep-red wavelength region. • High chemical stability suitable for long-term monitoring of lipid droplets. • Selective detection of lipid droplets under different cell conditions. [ABSTRACT FROM AUTHOR]