title: Uptake of imatinib-loaded polyelectrolyte complexes by BCR-ABL(+) cells: a long-acting drug-delivery strategy for targeting oncoprotein activity.
abstract: Imatinib mesylate (IM), a selective tyrosine kinase inhibitor of the oncoprotein BCR-ABL, is the 'gold standard' for patients with chronic myeloid leukemia (CML) but the drug does not eliminate CML stem cells, leading to disease relapse on drug discontinuation. At present, much effort is focused on delivery carriers that can increase the intracellular retention and antileukemic impact of IM. We previously validated IM-loaded polyelectrolyte microcapsules as effective purging agents to eradicate BCR-ABL(+) cells from CML patient autografts. The aim is to develop controlled release carriers that can increase the intracellular retention and functionality of IM in leukemia cells.
  
  
  METHODS
  Herein, novel polyelectrolyte complexes were used as model carriers for IM in a CML cell line (KU812) and CD34(+) cells freshly isolated from patients.
  
  
  CONCLUSIONS
  Polyelectrolyte complexes promoted a long-acting BCR-ABL kinase inactivation that was necessary to promote apoptosis at approximately twofold lower intracellular IM dose compared with the microscale formulation polyelectrolyte microcapsules.
  
  
  CONCLUSIONS
  IM-loaded polyelectrolyte complexes can be used as more efficient delivery devices for overcoming drug resistance of BCR-ABL(+) leukemic cells.
authors.affiliation: National Nanotechnology Laboratory, Institute of Nanoscience National Research Council, Via Arnesano, 73100 Lecce, Italy.
authors.forename: Ilaria E
authors.initials: IE
authors.lastname: Palamà
authors.forename: Addolorata M L
authors.initials: AM
authors.lastname: Coluccia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gigli
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004573:Electrolytes / Q000008:administration & dosage*; D016044:Fusion Proteins, bcr-abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics; D015513:Oncogene Proteins / Q000378:metabolism*; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D004573:Electrolytes; D015513:Oncogene Proteins; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL; chronic myeloid leukemia; drug delivery; drug resistance; imatinib mesylate; nanoscale delivery carrier; polyelectrolyte complex