Tetrahedron Probes for Ultrasensitive In Situ Detection of Telomerase and Surface Glycoprotein Activity in Living Cells.

In the present study, a tetrahedron probe with encoded internal reference nanoparticles (NPs) was self-assembled by a complementary nucleic acid aptamer for simultaneous ratiometric detection of telomerase (TE) and epithelial cell-adhesion molecule (EpCAM) in living cells. In the presence of a target, the dissociation of gold (Au) NPs, which was modified with corresponding tags, resulted in decreased surface-enhanced Raman scattering (SERS) signals. In addition, the ratios of Raman intensity at 1346 cm ^-1 /1096 cm ^-1 (TE) and 1614 cm ^-1 /1096 cm ^-1 (EpCAM) compared with the internal reference were demonstrated to quantify the level of TE and EpCAM, respectively, and can eliminate certain background noise. A good linear relationship was observed between them, and the linear range of TE and EpCAM in HeLa cells was 0.7 × 10 ^-12 to 37.5 × 10 ^-12 IU and 1.24 to 75.48 pg/mL with a limit of detection (LOD) of 7.6 × 10 ^-16 IU and 0.53 pg/mL, respectively, which were consistent with the results of Raman confocal imaging. Meanwhile, the versatility and specificity of the developed probes were confirmed in cell lines. These results provide a reliable and ultrasensitive strategy for the in situ detection of biomarkers and a new method for SERS-based tetrahedrons in the early diagnosis of cancer.