A near-infrared fluorescent probe with a self-immolative linker for rapid detection of beta-galactosidase and specific imaging of ovarian cancer cells

Abstract

Beta-galactosidase (β-gal) is a vital biological target which is widely used in the diagnosis of ovarian cancers. To date, only a few near-infrared fluorescent probes were successfully applied to monitor β-gal activity both in vitro and in vivo. However, these β-gal probes have disadvantages as poor water-solubility or slow response rate. To overcome these shortcomings, we constructed a novel near-infrared fluorescent probe (Cy-βgal) for β-gal tracing by using self-immolative group connected with fluorophore hemicyanine skeleton (Cy-OH) and recognition group (D-galactose). As expected, Cy-βgal displayed a fast response rate (8 min) to β-gal in water solution containing only 0.1 % DMSO with a fluorescent turn-on model. In addition, Cy-βgal exhibited favorable affinity (K_m = 23.51 μM) to β-gal accompanied with high catalytic efficiency (k_cat/K_m = 2.47 μM⁻¹ s⁻¹). Most importantly, Cy-βgal was able to specifically distinguish the ovarian cancer cells from lung cancer cells via the red fluorescence imaging signal of endogenous β-gal in living cells, implying that Cy-βgal has the potential for the diagnosis of ovarian cancer. It also confirmed that the self-immolative group-based designing strategy is a practical method for the rational design of other types of β-gal fluorescent probes.