Design of a selective and water-soluble fluorescent probe targeting Tau fibrils for intracellular and in vivo imaging

Tau protein has attracted much research interest in recent years. Development of effective techniques for in vivo imaging of Tau protein with high sensitivity and selectivity is of great importance. Herein, we rationally designed two novel, Tau-selective and AIE-active fluorescent probes (JL-3 and JL-6). Triphenylamine (TPA) as the AIE group, was first linked with a-CN group and N, N'-dimethylaminobenzene by 7C-7C conjugation to form a D-A-D structure. Then, a hydrophilic unit was conjugated to increase probe hydrophilicity. The AIE-activity and water -solubility characteristics contributed to larger Stokes shift and quantum yields, decreased background fluores-cence and therefore enhanced the signal-to-noise ratio of the detection. An excellent discrimination between Tau and beta-amyloid (A beta) aggregates (4.3-and 3.5-times higher Tau-over-A beta) was obtained on JL-3 and JL-6. Taking JL-3 as the example, an excellent linear relationship between Tau concentrations from 50 nM to 5 mu M and fluorescence was obtained (detection limit, 14.9 nM). Finally, JL-3 demonstrated a remarkable capacity for bioimaging in living cells, brain tissues and transgenic mice. Collectively, our results illustrated the potential of the developed probes as Tau-specific fluorescent dyes for both in vitro and in vivo applications.