Near-Infrared Fluorescence Probe with a New Recognition Moiety for Specific Detection and Imaging of Aldehyde Dehydrogenase Expecting the Identification and Isolation of Cancer Stem Cells.

Aldehyde dehydrogenase (ALDH) is a vital enzyme that converts aldehyde to acetic acid during alcohol metabolism. ALDH is also a cellular marker of cancer stem cells (CSCs), which plays an important role in cancer diagnosis and prognosis assessment. Therefore, there is a need to explore convenient, selective, and sensitive methods for the detection and imaging of ALDH. Because of the low background fluorescence and high penetration, near-infrared (NIR) fluorescent probes are powerful tools for the detection of ALDH. Until now, only one NIR fluorescent probe has been reported for detecting ALDH. Hence, we synthesized a novel NIR fluorescent probe, Probe-ALDH, by linking the new specific recognition moiety 4-hydroxymethyl benzaldehyde with NIR fluorophore AXPI. Compared with the existing ALDH fluorescent probes, Probe-ALDH has excellent properties, such as a new specific recognition moiety without the substitution of benzaldehyde, a simple synthesis method, emission wavelength in the NIR region, reaction time of only 30 min, and a detection limit as low as 0.03 U·mL-1, which is better than those of the previously reported probes. The probe effectively eliminates the interference from reactive oxygen species (ROS), amino acids, and amines. More importantly, the flow cytometry results showed that Probe-ALDH has great potential applications in the identification and isolation of CSCs. Ultimately, it was successfully applied to the imaging analysis of endogenous ALDH in HepG2 cells by the addition of inhibitor disulfiram. The excellent performance of Probe-ALDH makes it a promising candidate for drug discovery, cancer diagnosis, and so forth.