Daunorubicin-containing CLL1-targeting nanomicelles have anti-leukemia stem cell activity in acute myeloid leukemia

Tzu-Yin Lin, Yanjun Zhu, Yuanpei Li, Hongyong Zhang, Ai Hong Ma, Qilai Long, James Keck, Kit Lam, Chong-Xian Pan, Brian Jonas

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Patients with acute myeloid leukemia have a very poor prognosis related to a high rate of relapse and drug-related toxicity. The ability of leukemia stem cells (LSCs) to survive chemotherapy is primarily responsible for relapse, and eliminating LSCs is ultimately essential for cure. We developed novel disulfide-crosslinked CLL1-targeting micelles (DC-CTM), which can deliver high concentrations of daunorubicin (DNR) into both bulk leukemia cells and LSCs. Compared to free DNR, DC-CTM-DNR had a longer half-life, increased DNR area under the curve concentration by 11-fold, and exhibited a superior toxicity profile. In patient-derived AML xenograft models, DC-CTM-DNR treatment led to significant decreases in AML engraftment and impairment of secondary transplantation compared to control groups. Collectively, we demonstrate superior anti-LSC/AML efficacy, and preferable pharmacokinetic and toxicity profiles of DC-CTM-DNR compared to free DNR. DC-CTM-DNR has the potential to significantly improve treatment outcomes and reduce therapy-related morbidity and mortality for patients with AML.

Original languageEnglish (US)
Article number102004
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume20
DOIs
StatePublished - Aug 1 2019

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Keywords

  • AML
  • CLL1
  • Daunorubicin
  • Leukemia stem cells
  • Nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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