title: Synthesis of nanodiamond-daunorubicin conjugates to overcome multidrug chemoresistance in leukemia.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Mechanical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL, USA.
authors.forename: Han B
authors.initials: HB
authors.lastname: Man
authors.affiliation: Department of Mechanical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL, USA.
authors.forename: Hansung
authors.initials: H
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Ho-Joong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Mechanical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Robinson
authors.affiliation: Department of Mechanical Engineering, Robert R. McCormick School of Engineering and Applied Science, Northwestern University, Evanston, IL, USA.
authors.forename: Wing Kam
authors.initials: WK
authors.lastname: Liu
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Edward Kai-Hua
authors.initials: EK
authors.lastname: Chow
authors.affiliation: 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.
authors.forename: Dean
authors.initials: D
authors.lastname: Ho
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D002470:Cell Survival; D003630:Daunorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy*; D056004:Molecular Dynamics Simulation; D058612:Nanodiamonds / Q000737:chemistry*; D050997:Nanomedicine; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D058612:Nanodiamonds; D003630:Daunorubicin
keywords: Chemoresistance; Drug delivery; Leukemia; Nanodiamond; Nanomedicine
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