Coupled delivery of imatinib mesylate and doxorubicin with nanoscaled polymeric vectors for a sustained downregulation of BCR-ABL in chronic myeloid leukemia. (26th September 2014) - Palamà, Ilaria E.
Abstract : Our couple delivery strategy allowed a sustained downregulation of BCR-ABL for long times in chronic myeloid leukemia, combining two types of polymeric nanoparticles for quick and slow release of IM and DOX. Abstract : 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 nanoparticles 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.