Abnormal changes in numbers, sizes and polarities of lipid droplet (LD) are thought to be closely associated with varieties diseases such as fatty liver, diabetes, atherosclerosis and even cancer. However, there still exists some shortcomings of the current commercial LD probes, such as aggregation-caused quenching (ACQ) effect, small Stokes shifts, excitation wavelength restricted to visible light region, and lacking of two-photon excitation fluorescence, which restrict the diagnosis of LD related diseases. Herein, a two-photon aggregation-induced emission (AIE) bioprobe, namely TP-LDP, was rationally designed by constructing of the donor-acceptor-donor (D-A-D) structure for specific imaging of LD. TP-LDP exhibited AIE-activities, solvatochromic emissions (λemmax: 451–652 nm), extra-large Stokes shifts (11550 cm−1) as well as two-photon absorption ability (156 GM). More importantly, cellular experiments demonstrated that TP-LDP possessed excellent photostability, nice two-photon excited fluorescence imaging ability as well as precise LD-targeting, and successfully detected abnormal LD proliferations in living cells. These features enable TP-LDP to effectively compensate for the shortcomings of commercial LD dyes and have the potential to become a powerful tool for detecting LD related diseases.
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