title: Epirubicin-adsorbed nanodiamonds kill chemoresistant hepatic cancer stem cells.
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.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore , 117597 Singapore.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Xinyi Casuarine
authors.initials: XC
authors.lastname: Low
authors.forename: Weixin
authors.initials: W
authors.lastname: Hou
authors.forename: Lissa Nurrul
authors.initials: LN
authors.lastname: Abdullah
authors.forename: Tan Boon
authors.initials: TB
authors.lastname: Toh
authors.forename: Masturah
authors.initials: M
authors.lastname: Mohd Abdul Rashid
authors.forename: Dean
authors.initials: D
authors.lastname: Ho
authors.forename: Edward Kai-Hua
authors.initials: EK
authors.lastname: Chow
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015251:Epirubicin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000473:pathology*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D058612:Nanodiamonds / Q000737:chemistry*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010316:Particle Size; D011506:Proteins / Q000737:chemistry; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D058612:Nanodiamonds; D011506:Proteins; D015251:Epirubicin
keywords: biomaterials; cancer stem cell; chemoresistance; drug delivery; nanodiamond; nanomedicine