Galactose-imidazole mediated dual-targeting fluorescent probe for detecting Fe3+ in the lysosomes of hepatocytes: Design, synthesis and evaluation

In this work, three novel dual-targeting fluorescent probes were designed with modification by imidazole and one galactose (IM-Gal-1), by imidazole and two galactoses (IM-Gal-2), and by imidazole and three galactoses (IM-Gal-3), separately. These probes showed good selectivity and sensitivity toward Fe3+ with 1:2 stoichiometry recognition mode. The detection limits toward Fe3+ were (1.293 ± 0.005) × 10-7 M for IM-Gal-1, (7.735 ± 0.005) × 10-8 M for IM-Gal-2, and (1.325 ± 0.023) × 10-7 M for IM-Gal-3. These low-toxic probes exhibited excellent hepatic targeting capacity, which is attributed to the specific recognition of asialoglycoprotein receptor (ASGPR) overexpressed on hepatocytes by the galactose group of probes. The hepatic targeting capacity followed IM-Gal-1 < IM-Gal-2< IM-Gal-3 trend due to the galactose cluster effect. Under the attraction between acidic lysosome and basic imidazole group, these imidazole-modified probes were confirmed to possess good lysosome-targeting capacities, earlier demonstrating imidazole as a lysosome-targeting group. Overall, these dual-targeting probes co-modified by galactose and imidazole exhibited unique advantages in precise diagnosis and treatment of liver lysosomal iron-related diseases.