Novel Hexosaminidase-Targeting Fluorescence Probe for Visualizing Human Colorectal Cancer

Precise tumor diagnosis and evaluation of disease extent are crucial for treatment of solid cancers. In order to complement the limited ability of the unaided human eye to discriminate tumor tissue and normal tissue, we have developed a series of fluorescence probes activatable specifically in cancer tissues. Here, we describe the design, synthesis, and application of a new fluorescence probe targeting hexosaminidase (HMRef-βGlcNAc), which is located in lysosomes and is overexpressed in several carcinomas, including colorectal cancer. This probe could sensitively detect intracellular hexosaminidase activity in human colorectal cancer cell lines, and could visualize tiny metastatic nodules (smaller than 1 mm) in a mouse model of disseminated human peritoneal colorectal cancer (HCT116). In human colorectal cancer specimens obtained at surgery, the probe showed high tumor sensitivity/specificity, together with a high tumor-to-normal signal ratio. HMRef-βGlcNAc is a promising candidate for clinical application during surgical or endoscopic procedures to treat colorectal cancer.