title: Curcumin-derivative nanomicelles for the treatment of triple negative breast cancer.
abstract: BACKGROUND
  Triple negative breast cancer (TNBC) is a subtype of breast cancer characterized by its poor outcome and a lack of targeted therapies. Recently, our laboratory has developed a second generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71) that shows potent in vitro cytotoxicity. RL71 is hydrophobic with poor bioavailability which limits its clinical development.
  
  
  OBJECTIVE
  We have designed styrene-co-maleic acid (SMA) micelles encapsulating 5, 10 or 15% RL71 by weight/weight ratio to improve its solubility and pharmacokinetic profile.
  
  
  METHODS
  The micelles charge, size and release rate were characterized. We evaluated their cytotoxicity against TNBC cell lines. The internalization of the drug inside the cells was measured by HPLC and the efficiency of the micelles was tested using a tumor spheroid model.
  
  
  RESULTS
  The micelles exhibited mean diameters of 125-185 nm and had a neutral charge. SMA-RL71 micelles have a cytotoxicity profile comparable to the free drug against several TNBC cell lines. Moreover, the 15% loaded micelles increased the stability of RL71 and demonstrated higher activity in a tumor spheroid model.
  
  
  CONCLUSIONS
  The current study demonstrates the efficiency of SMA for drug delivery, the influence of physicochemical characteristics on cytotoxicity, and provides the basis for preclinical testing in vivo.
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Taurin
authors.forename: Hayley
authors.initials: H
authors.lastname: Nehoff
authors.forename: Jasper
authors.initials: J
authors.lastname: Diong
authors.forename: Lesley
authors.initials: L
authors.lastname: Larsen
authors.forename: Rhonda J
authors.initials: RJ
authors.lastname: Rosengren
authors.forename: Khaled
authors.initials: K
authors.lastname: Greish
mesh_terms: D045744:Cell Line, Tumor; D003474:Curcumin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008823:Micelles; D036103:Nanotechnology; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D008823:Micelles; D003474:Curcumin