Design, synthesis and biological evaluation of novel dual-targeting fluorescent probes for detection of Fe3+ in the lysosomes of hepatocytes mediated by galactose-morpholine moieties

In this work, novel dual-targeting probes composed of galactose and morpholine were designed and synthesized for monitoring Fe3+ levels in the lysosome of hepatocyte. MP-Gal-1, MP-Gal-2 and MP-Gal-3 showed good selectivity and sensitivities toward Fe3+ with the detection limits of 9.40 × 10-8 M, 7.68 × 10-8 M and 7.10 × 10-8 M, respectively. 1:2 stoichiometry is the most likely recognition mode between probe and Fe3+. Low toxic MP-Gal-1, MP-Gal-2 and MP-Gal-3 exhibited favorable hepatic targeting effect in both cell and tissue levels, which was because the galactose group of probe could be recognized by ASGPR overexpressed on the hepatocytes. The hepatocyte-targeting capacity followed MP-Gal-1 < MP-Gal-2 < MP-Gal-3 trend, which was attributed to the galactose cluster effect. MP-Gal-1, MP-Gal-2 and MP-Gal-3 also displayed good lysosomes-targeting capacities, because the basic morpholine moiety of probes could be easily attracted by the acidic lysosome. Therefore, MP-Gal-1, MP-Gal-2 and MP-Gal-3 have good dual targeting capacities (liver and lysosome) and could be used to detect lysosomal Fe3+ in the liver, which is great significant for precise diagnosis and treatment of liver lysosomal iron-related diseases.