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Nanomedicine. 2014 Feb;10(2):359-69. doi: 10.1016/j.nano.2013.07.014. Epub 2013 Aug 3.

Synthesis of nanodiamond-daunorubicin conjugates to overcome multidrug chemoresistance in leukemia.

Author information

1
Department of Mechanical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL, USA.
2
Division of Oral Biology and Medicine, Division of Advanced Prosthodontics, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, California NanoSystems Institute, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
3
Cancer Science Institute of Singapore, National University of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
4
Division of Oral Biology and Medicine, Division of Advanced Prosthodontics, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, California NanoSystems Institute, and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: csikce@nus.edu.sg.

Abstract

Nanodiamonds (NDs) are promising candidates in nanomedicine, demonstrating significant potential as gene/drug delivery platforms for cancer therapy. We have synthesized ND vectors capable of chemotherapeutic loading and delivery with applications towards chemoresistant leukemia. The loading of Daunorubicin (DNR) onto NDs was optimized by adjusting reaction parameters such as acidity and concentration. The resulting conjugate, a novel therapeutic payload for NDs, was characterized extensively for size, surface charge, and loading efficiency. A K562 human myelogenous leukemia cell line, with multidrug resistance conferred by incremental DNR exposure, was used to demonstrate the efficacy enhancement resulting from ND-based delivery. While resistant K562 cells were able to overcome treatment from DNR alone, as compared with non-resistant K562 cells, NDs were able to improve DNR delivery into resistant K562 cells. By overcoming efflux mechanisms present in this resistant leukemia line, ND-enabled therapeutics have demonstrated the potential to improve cancer treatment efficacy, especially towards resistant strains.

FROM THE CLINICAL EDITOR:

The authors of this study demonstrate superior treatment properties of resistant leukemia cell lines by utilizing nanodiamond vectors loaded with daunorubicin, paving the way to clinical studies in the hopefully not too distant future.

KEYWORDS:

Chemoresistance; Drug delivery; Leukemia; Nanodiamond; Nanomedicine

PMID:
23916889
PMCID:
PMC3912225
DOI:
10.1016/j.nano.2013.07.014
[Indexed for MEDLINE]
Free PMC Article
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