Development of fluorescent probes for use in cancer imaging is one of the widely studied research areas.  Fluorescence based molecular imaging provides a great advantage for cancer diagnosis due to its high sensitivity and noninvasiveness, compared to conventional methods used in clinics. Several molecular probes have been developed during last decades for a high-resolution imaging with ultra-low background signals. In order to satisfy cancer cell selectivity, a popular approach is to design activity-based fluorescent probes, which emit light only in the cancer cells, while staying deactivated in normal cells. Many cancer types overexpress specific biomarkers that can be utilized as a promoter in activatable probes. Thus, these imaging probes are designed to provide the imaging signals upon specific biomarker recognition. This happens due to a chemical reaction between the probe and biomarker of interest to generate an “activated sensor”, which is fluorescent upon irradiation with an external light. Enzymes are recognized as promising biomarkers, having high expression levels in certain cancer types compared to their healthy counterparts. Detection of these enzymes require the molecular probes acting as artificial substrates. However, use of only one enzyme might yield in false positive signals coming from the healthy cells. To that end, an additional selection criterion is one of the best options. Thus, in this study we introduce a red-emitting fluorescent probe (<b>RAM</b>), which can be selectively activated by two enzymes that are overexpressed in liver cancer cells. The synthesis of the probe has been completed successfully. <b>RAM</b> exhibits a turn-on fluorescence signal only in the presence of both enzymes, thus follows an AND molecular logic gate operation. On the other side, no emission signal was detected in normal cells, suggesting high selectivity towards cancer cells.

Dual enzyme activatable fluorescent probes towards selective imaging of liver cancer cells

ACS Spring 2022

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