Barbara Klajnert-Maculewicz
University of Lodz, Poland
Title: Sugar-modified PPI dendrimers as carriers of anti-leukemia drugs
Biography
Biography: Barbara Klajnert-Maculewicz
Abstract
Anticancer drugs such as cytarabine (araC) belong to nucleoside analogues (NAs). NAs are commonly used in the treatment of acute myeloid leukemia, acute lymphocytic leukemia, and lymphomas. AraC acts by interfering with newly synthesized nucleic acids or by modifying physiological nucleosides metabolism. Like most nucleoside analogs, araC is administered as an inactive prodrug and requires specialized nucleoside transporters to cross plasma membranes. Inside a cell, araC is activated to cytotoxic 5’-triphosphates form (araCTP) by intracellular kinases. Unfortunately, a therapy based on cytarabine has its limitations due to several primary and acquired resistance mechanisms that arise during prodrug activation steps. It may lead to inefficient concentration of the therapeutics in cancer cells. Carrier systems that would deliver active forms of NAs are currently seeking. It has been demonstrated that polypropylene imine (PPI) dendrimers with a partially modified surface by maltose residues (PPI-m) easily form complexes with negatively charged 5’-triphosphates of nucleoside analogues. It happens due to the presence of protonated primary and tertiary amino groups. PPI-m dendrimers are non-toxic and highly biocompatible. Moreover, PPI-m dendrimers protect bound drug molecules from enzymatic degradation. Complexes of araCTP and PPI-m dendrimers show enhanced cytotoxic activity against an acute myeloid lukemia cell line 1301 in comparison with free cytarabine and 5’-triphosphate of cytarabine. Thus, PPI-m dendrimers improve stability of NAs and efficiently deliver the active drug forms directly to cancer cells. To sum up, maltose-modified polypropylene imine dendrimers are attractive systems as anticancer drug carriers, especially with a vision to apply them when drug-resistance occurs.