ИСТИНА

According to the WHO, the hepatocellular carcinoma (HCC, liver cancer) is the 5th most common and the second most deadly disease among human malignant tumors[1]. Modern drugs used for chemotherapy have a number of serious shortcomings, which can be overcome using the targeted drug delivery (TDD) to the tumor cells. A promising target for a delivery to hepatocytes is the acialoglycoprotein receptor selectively recognizing galactose derivatives[2]. Asialoglycoprotein receptor (ASGP-R) belongs to a wide family of C-type lectins and it is currently regarded as an attractive protein in the field of targeted drug delivery. It is abundantly expressed in hepatocytes and can be found predominantly on the sinusoidal surface especially of HepG2 cells. Therefore, ASGP-R can be used for the TDD of anticancer therapeutics against HCC and molecular diagnostic tools. We have synthesized trivalent ligands with the structure shown below. These ligands have higher affinity for the receptor than the native ligand N-acethylgalactosamine. This effect is based on the peculiarities of the receptor’s structure[3] and the cumulative binding effect[4]. Then ligands were conjugated to antineoplastic agents (paclitaxel and gemcitabine) used in clinical practice