Design, synthesis and biological evaluation of novel dual-targeting fluorescent probes for detection of Fe 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 Fe levels in the lysosome of hepatocyte. MP-Gal-1, MP-Gal-2 and MP-Gal-3 showed good selectivity and sensitivities toward Fe with the detection limits of 9.40 × 10 M, 7.68 × 10 M and 7.10 × 10 M, respectively. 1:2 stoichiometry is the most likely recognition mode between probe and Fe. 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 Fe in the liver, which is great significant for precise diagnosis and treatment of liver lysosomal iron-related diseases.