A hemicyanine-based fluorescent probe for simultaneous imaging of Carboxylesterases and Histone deacetylases in hepatocellular carcinoma

Carboxylesterases (CESs) and Histone deacetylases (HDACs) are regarded as important signaling enzymes highly associated with the development and progression of multiple cancers, including hepatocellular carcinoma (HCC). In this work, a near-infrared (NIR) fluorescent probe named Lys-HXPI was designed and synthesized, which linked a hemicyanine dye and 6-acetamidohexanoic acid via an ester bond. Lys-HXPI displayed a remarkable increase with a NIR emission at 720 nm, a low detection limit (<10 nM) for HDAC1, HDAC 6, CES1 and CES2, as well as a high selectivity for the target enzymes over other relevant analytes. Furthermore, Lys-HXPI was used to image endogenous target enzymes in living cells, tumor-bearing nude mice and tissue slices. The ability of Lys-HXPI to simultaneous image CESs and HDACs was demonstrated with RT-qPCR and the confocal imaging in Hep G2 and MDA-MB-231. Taking advantage of NIR emission, the probe was also successfully applied to imaging Hep G2 tumor mice and tissue slices. Lys-HXPI is expected to be useful for the effective detecting of CESs and HDACs in complex biosystems.