1. Epirubicin-adsorbed nanodiamonds kill chemoresistant hepatic cancer stem cells.
- Author
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Wang X, Low XC, Hou W, Abdullah LN, Toh TB, Mohd Abdul Rashid M, Ho D, and Chow EK
- Subjects
- Animals, Antineoplastic Agents chemistry, Antineoplastic Agents metabolism, Antineoplastic Agents pharmacology, Biological Transport, Cell Line, Tumor, Cell Proliferation drug effects, Drug Carriers chemistry, Drug Liberation, Epirubicin metabolism, Humans, Hydrogen-Ion Concentration, Mice, Models, Molecular, Molecular Conformation, Neoplastic Stem Cells metabolism, Particle Size, Proteins chemistry, Surface Properties, Drug Resistance, Neoplasm drug effects, Epirubicin chemistry, Epirubicin pharmacology, Liver Neoplasms pathology, Nanodiamonds chemistry, Neoplastic Stem Cells drug effects, Neoplastic Stem Cells pathology
- Abstract
Chemoresistance is a primary cause of treatment failure in cancer and a common property of tumor-initiating cancer stem cells. Overcoming mechanisms of chemoresistance, particularly in cancer stem cells, can markedly enhance cancer therapy and prevent recurrence and metastasis. This study demonstrates that the delivery of Epirubicin by nanodiamonds is a highly effective nanomedicine-based approach to overcoming chemoresistance in hepatic cancer stem cells. The potent physical adsorption of Epirubicin to nanodiamonds creates a rapidly synthesized and stable nanodiamond-drug complex that promotes endocytic uptake and enhanced tumor cell retention. These attributes mediate the effective killing of both cancer stem cells and noncancer stem cells in vitro and in vivo. Enhanced treatment of both tumor cell populations results in an improved impairment of secondary tumor formation in vivo compared with treatment by unmodified chemotherapeutics. On the basis of these results, nanodiamond-mediated drug delivery may serve as a powerful method for overcoming chemoresistance in cancer stem cells and markedly improving overall treatment against hepatic cancers.
- Published
- 2014
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