Deferasirox derivative-based fluorescent probes for the potential diagnosis and therapy of iron overload-induced hepatocellular carcinoma by cellular and zebrafish experiments

• A novel hepatocellular carcinoma targeted deferasirox derivative ExPh 2 -CNAc 2 with AIE properties was designed. • ExPh 2 -CNAc 2 can achieves iron overload treatment through carboxylesterase activation. • The “hydrolysis-chelation” process of ExPh 2 -CNAc 2 is characterized by multiple fluorescence changes. • ExPh 2 -CNAc 2 may have promising applications in HCC treatment. The association of excess iron in humans with the incidence and proliferation of hepatocellular carcinoma (HCC) has been confirmed by numerous studies. In this case, developing a fluorescent probe that can both target HCC and eliminates excess iron in HCC is extremely meaningful. To accomplish these goals, a fluorescent probe ExPh 2 -CNAc 2 was designed and synthesized, which can be selectively hydrolyzed by carboxylesterases (CE), one kind of biomarker in HCC. The fluorescent parent ExPh 2 -CN with unique aggregation-induced emission (AIE) and iron-chelating properties of deferasirox derivatives generated by CE hydrolysis of ExPh 2 -CNAc 2 can further chelate with Fe (III) and target HCC for the treatment of iron excess, and the whole process can be effectively monitored by fluorescence changes. Furthermore, the potential for CE imaging and Fe (III) overload resolution of ExPh 2 -CNAc 2 is demonstrated by experiments in cells and zebrafish at different growth stages. The superior in vivo imaging and chelation properties of the probe ExPh 2 -CNAc 2 may provide a new avenue for the diagnosis and treatment of HCC in iron overloaded patients.