Zhou, P., Hatziieremia, S., Elliott, M. A., Scobie, L., Crossan, C., Michie, A. M. , Holyoake, T. L., Halbert, G. W. and Jorgensen, H. 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. (doi: 10.1016/j.jconrel.2010.09.016)
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Publisher's URL: http://dx.doi.org/10.1016/j.jconrel.2010.09.016
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<sup>+</sup>38<sup>lo/−</sup>), are significantly lower than in CML progenitor cells (total CD34<sup>+</sup>) 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<sup>+</sup> and primitive CD34<sup>+</sup>38<sup>lo/−</sup> cells accumulated significantly higher levels of sLDL when compared with non-CML CD34<sup>+</sup> cells. Thus, drug-loading the sLDL nanoparticles could potentially enhance intracellular drug concentrations in primitive CML cells and thus aid their eradication.
| Item Type: | Articles |
|---|---|
| Additional Information: | NOTICE: this is the author’s version of a work that was accepted for publication in <i>Journal of Controlled Release</i>. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in <i>Journal of Controlled Release</i>, [148, 3, (2010)] DOI:10.1016/j.jconrel.2010.09.016 |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Michie, Professor Alison and Holyoake, Professor Tessa and Crossan, Miss Claire and Jorgensen, Dr Heather and Zhou, Mr Peixun and Scobie, Dr Linda and Hatziieremia, Dr Sophia |
| Authors: | Zhou, P., Hatziieremia, S., Elliott, M. A., Scobie, L., Crossan, C., Michie, A. M., Holyoake, T. L., Halbert, G. W., and Jorgensen, H. G. |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
| Journal Name: | Journal of Controlled Release |
| Publisher: | Elsevier |
| ISSN: | 0168-3659 |
| ISSN (Online): | 1873-4995 |
| Published Online: | 22 September 2010 |
| Copyright Holders: | Copyright © 2010 Elsevier |
| First Published: | First published in Journal of Controlled Release 148(3):380-387 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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