Coupled delivery of imatinib mesylate and doxorubicin with nanoscaled polymeric vectors for a sustained downregulation of BCR-ABL in chronic myeloid leukemia

In this work, we have investigated the potential benefits of combining biodegradable pH sensitive core-shell PCL NPs loaded with IM and enzyme sensitive polyelectrolyte complexes (PECs) loaded with doxorubicin (DOX). Our in vitro studies confirmed the excellent antileukemic activity of dual drug loaded nano-particles on CML cells. As compared with a drug alone, co-treatment with IM and DOX loaded in nanoparticles allowed a sustained downregulation of BCR-ABL and significant CML stem cell death. This furthermore showed that couple formulation of nanoparticles enhanced the drugs' kinetics and efficacy, combined with the pH sensibility of core-shell PCL NPs loaded with IM and enzyme sensitive polyelectrolyte complexes (PECs) loaded with DOX. Our study demonstrates that dual drug loaded nanoparticles work in a synergistic manner, lowering the dose and confirming that both drugs reach the target cell specifically, maximizing the cytotoxicity while minimizing the chances of cell resistance to any one drug.