In vivo imaging of beta-galactosidase stimulated activity in hepatocellular carcinoma using ligand-targeted fluorescent probe

Abstract

Development of targeted, selective, and noninvasive fluorescent probes for in vivo visualization of tumor-associated overexpressed enzymes are highly anticipated for cancer diagnosis and therapy. Herein, we developed a noninvasive fluorescent probe (DCDHF-beta gal) for the sensitive detection, and in vivo visualization of beta-galactosidase in hepatocyte HepG2 cells and its xenograft model. As a model system for in vivo targeted imaging, DCDHF-beta gal possessing galactose unit selectively target hepatocyte and monitor the beta-galactosidase activity with deep tissue penetration, and low background interference. DCDHF-beta gal was activated by intracellular beta-galactosidases as the driving force for the release of NIR fluorophore, thereby exhibiting ratiometric optical response. Initial fluorescence emission measured at 615 nm was changed to fluorescence at 665 nm upon activation of DCDHF-beta gal with beta-galactosidase. Ratiometric fluorescence detection of beta-galactosidase was also observed in hepatocellular carcinoma cells and tumor xenograft. The noninvasive in vivo optical imaging facilitated by targeted and enzyme activated imaging agent would be useful in various biomedical and diagnostic applications. (C) 2017 Elsevier Ltd. All rights reserved.