N-(2-Hydroxypropyl)methacrylamide Copolymer-Drug Conjugates for Combination Chemotherapy of Acute Myeloid Leukemia

There is a need for new treatment strategies of acute myeloid leukemia (AML). In this study, four different drugs, including cytarabine, daunorubicin, GDC-0980, and JS-K, were investigated in vitro for the two-drug combinations treatment of AML. The results revealed that cytarabine and GDC-0980 had the strongest synergism. In addition, cell cycle analysis was conducted to investigate the effect of the different combinations on cell division. For future in vivo application, N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cytarabine and GDC-0980 conjugates were synthesized, respectively. In vitro studies demonstrated that both conjugates had potent cytotoxicity and their combination also showed strong synergy, suggesting a potential chemotherapeutic strategy for future AML treatment. Four different drugs, including cytarabine, daunorubicin, GDC-0980, and JS-K, are used for two-drug combination treatment against acute myeloid leukemia. Combining cytarabine with GDC-0980 shows the strongest synergistism. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-cytarabine/GDC-0980 conjugates are synthesized. They also hve potent cytotoxicity and strong synergstism in combination.