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

Nanomedicine

Department of Internal Medicine, University of California Davis, Sacramento, CA 95817, USA; VA Northern California Health Care System, Mather, CA.. Electronic address:

Published: August 2019

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237247PMC
http://dx.doi.org/10.1016/j.nano.2019.04.007DOI Listing

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