Design and synthesis of esterase-activated fluorescent probe for diagnosis and surgical guidance of liver cancer.

Liver cancer seriously threatens the health of human beings. Studies have found that esterase is overexpressed in liver cancer cells. Therefore, esterase can be one of the biomarkers of liver cancer. Previous literature studies have shown that the structures of fluorescent probe detection groups significantly impact the probes themselves and enzyme detection. In this paper, three "off-on" esterase-activated fluorescent probes (RHO-1, RHO-2 and RHO-3) with different length of the carbon chains of the detection groups were designed and synthesized. Density functional theory (DFT) calculation and Michaelis-Menten equations were applied to study the optical properties and affinity with esterase of the probes. Compared with RHO-1 and RHO-2, RHO-3 showed superior optical properties and affinity with esterase. Subsequently, RHO-3 was further used to detect esterase activity in vitro and in vivo. RHO-3 was the first esterase-activated fluorescent probe applied to image-guided diagnosis and surgical resection of liver cancer. It was expected to be a promising molecular imaging diagnostic tool in clinical applications.