title: Coupled delivery of imatinib mesylate and doxorubicin with nanoscaled polymeric vectors for a sustained downregulation of BCR-ABL in chronic myeloid leukemia.
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.
authors.affiliation: Institute Nanoscience CNR (NNL, CNR-NANO) via Arnesano, Lecce, Italy. ilariaelena.palama@nano.cnr.it.
authors.forename: Ilaria E
authors.initials: IE
authors.lastname: Palamà
authors.forename: Barbara
authors.initials: B
authors.lastname: Cortese
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Amone
authors.forename: Valentina
authors.initials: V
authors.lastname: Arcadio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gigli
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D063566:Biodegradable Plastics / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology*; D000068877:Imatinib Mesylate / Q000737:chemistry / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry*; D000071228:Polyelectrolytes / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D063566:Biodegradable Plastics; D000960:Hypolipidemic Agents; D000071228:Polyelectrolytes; D011108:Polymers; D004317:Doxorubicin; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl