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Uptake of synthetic low density Lipoprotein by leukemic stem cells--a potential stem cell targeted drug delivery strategy

Zhou, Peixun and Hatziieremia, Sophia and Elliott, Moira A and Scobie, Linda and Crossan, Claire and Michie, Alison M and Holyoake, Tessa L and Halbert, Gavin W and Jørgensen, Heather G (2010) Uptake of synthetic low density Lipoprotein by leukemic stem cells--a potential stem cell targeted drug delivery strategy. Journal of Controlled Release, 148 (3). pp. 380-387.

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Abstract

Chronic Myeloid Leukemia (CML) stem/progenitor cells, which over-express Bcr-Abl, respond to imatinib by a reversible block in proliferation without significant apoptosis. As a result, patients are unlikely to be cured owing to the persistence of leukemic quiescent stem cells (QSC) capable of initiating relapse. Previously, we have reported that intracellular levels of imatinib in primary primitive CML cells (CD34+38(lo/⁻)), are significantly lower than in CML progenitor cells (total CD34+) and leukemic cell lines. The aim of this study was to determine if potentially sub-therapeutic intracellular drug concentrations in persistent leukemic QSC may be overcome by targeted drug delivery using synthetic Low Density Lipoprotein (sLDL) particles. As a first step towards this goal, however, the extent of uptake of sLDL by leukemic cell lines and CML patient stem/progenitor cells was investigated. Results with non-drug loaded particles have shown an increased and preferential uptake of sLDL by Bcr-Abl positive cell lines in comparison to Bcr-Abl negative. Furthermore, CML CD34+ and primitive CD34+38(lo/⁻) cells accumulated significantly higher levels of sLDL when compared with non-CML CD34+ cells. Thus, drug-loading the sLDL nanoparticles could potentially enhance intracellular drug concentrations in primitive CML cells and thus aid their eradication.

Item type: Article
ID code: 32629
Notes: Copyright © 2010 Elsevier B.V. All rights reserved.
Keywords: antigens, antineoplastic agents, cell line, cell membrane permeability, cells, drug delivery systems, hematopoietic stem cells, leukemia, leukocytes, lipoproteins, neoplastic stem cells, low density lipoprotein, chronic myeloid leukemia , CD34+, hemopoietic stem cells, nanoparticle, Therapeutics. Pharmacology, Pharmaceutical Science
Subjects: Medicine > Therapeutics. Pharmacology
Department: Faculty of Engineering > Naval Architecture and Marine Engineering
Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 19 Aug 2011 11:53
    Last modified: 11 Apr 2014 08:20
    URI: http://strathprints.strath.ac.uk/id/eprint/32629

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