A glycocluster strategy to develop dual-cascade targeting fluorescence probe detecting Fe3+ in hepatocyte mitochondria

Abstract

Many diseases are closely related to the level of Fe3 + which mainly stored in the liver of human body, and mitochondria is the dominant organelle for iron metabolism. In this work, based on a glycocluster strategy, three novel dual-cascade targeting (hepatocyte and mitochondria) fluorescent probes were designed to monitor Fe3+ in hepatic mitochondria with good selectivity and sensitivity. Low toxic glycosylated probes exhibited obvious hepatic-targeting capacity in vitro and in vivo, since the galactose residue of probes confer highly affinity to asialoglycoprotein receptor (ASGPR) specifically expressed on the membrane of hepatocytes. Moreover, the hepatic targeting ability presented a trend of TP-Gal-1 < TP-Gal-2 < TP-Gal-3, which may be ascribed to a “cluster effect” of galactose-recognition toward ASGPR. Besides, the aimed probes displayed favorable mitochondria-targeting capacity under the assistance of electropositive triphenylphosphine. Overall, these galactosylated probes with dual-cascade targeting capacity provided promising detected tools for Fe3 + in hepatocyte mitochondria, which is greatly important for precise diagnosis and insight into liver mitochondrial Fe3 + -related diseases.