Protein Nanomedicine Exerts Cytotoxicity toward CD34+ CD38- CD123+ Leukemic Stem Cells

Parwathy Chandran; Keechilat Pavithran; Neeraj Sidharthan; Abhilash Sasidharan; Shantikumar Nair; Manzoor Koyakutty

doi:10.1021/acsbiomaterials.5b00361

Protein Nanomedicine Exerts Cytotoxicity toward CD34⁺ CD38^- CD123⁺ Leukemic Stem Cells

ACS Biomater Sci Eng. 2015 Dec 14;1(12):1194-1199. doi: 10.1021/acsbiomaterials.5b00361. Epub 2015 Nov 3.

Authors

Parwathy Chandran¹, Keechilat Pavithran², Neeraj Sidharthan², Abhilash Sasidharan¹, Shantikumar Nair¹, Manzoor Koyakutty¹

Affiliations

¹ Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham University, Kochi, Kerala 682041, India.
² Department of Medical Oncology, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala 682041, India.

PMID: 33429669
DOI: 10.1021/acsbiomaterials.5b00361

Abstract

The efficacy of protein-vorinostat nanomedicine (NV) is demonstrated in leukemic stem cells (LSC) isolated from refractory acute myeloid leukemia (AML) patient samples, where it successfully ablated both CD34⁺ CD38^- CD123⁺ LSC and non-LSC "leukemic blast" compartments, without inducing myelosuppression or hemotoxicity. Besides, NV also exerted excellent synergistic lethality against leukemic bone marrow cells (BMC) at lower concentrations (0.1 μM) in combination with DNA methyltransferase (DNMT) inhibitor, decitabine. Considering the extermination of resilient LSC and synergism with decitabine, NV shows promise for clinical translation in the setting of a more tolerable and effective epigenetic targeted therapy for leukemia.

Keywords: acute myeloid leukemia; cancer stem cells; decitabine; leukemic stem cells; protein-vorinostat nanomedicine.