Uptake of synthetic Low Density Lipoprotein by leukemic stem cells: a potential stem cell targeted drug delivery strategy

Peixun Zhou, Sophia Hatziieremia, Moira A. Elliott, Linda Scobie, Claire Crossan, Alison M. Michie, Tessa L. Holyoake, Gavin W. Halbert, Heather G. Jørgensen

Research output: Contribution to journalArticle

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+38lo/-), 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.

Original languageEnglish
Pages (from-to)380-387
Number of pages8
JournalJournal of Controlled Release
Volume148
Issue number3
DOIs
Publication statusPublished - 1 Dec 2010

Keywords

  • stem cells
  • leukemia
  • Low Density Lipoprotein

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