Research

Epirubicin-Adsorbed Nanodiamonds Kill Chemoresistant Hepatic Cancer Stem Cells (ACS Nano, Dec 2014)

Xin Wang , Xinyi Casuarine Low , Weixin Hou ,Lissa Nurrul Abdullah , Tan Boon Toh , Masturah Mohd Abdul Rashid , Dean Ho §, and Edward Kai-Hua Chow *†‡

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597Singapore

Cancer Science Institute of Singapore, Yong Loo Lin School of Medicine, National University of Singapore, 117599 Singapore

§ 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, California 90095, United States

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 vivocompared 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.

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Schematic model showing surfance and chemical structure of nanodiamond (ND) and Epirubicin (Epi), synthesis and aggregation of EPND. ND represented in truncated octahedron structure with different surface charge denoted with colour. ND surface functional group indicated, including benzene ring, carboxyl group and hydrogen group. Molecular skeleton representing carbon, oxygen and nitrogen atoms in Epi molecule was shown in red. Synthesis of EPND was performed under basic condition of 2.5mM NaOH through physical adsorption between Epi and ND. Aggregation around 90mm was formed after EPND synthesis.