title: The Use of Styrene Maleic Acid Nanomicelles Encapsulating the Synthetic Cannabinoid Analog WIN55,212-2 for the Treatment of Cancer.
abstract: Synthetic cannabinoid WIN55,212-2 (WIN) has shown a promise as an anticancer agent but causes psychoactive side-effects. In the present study, nano-micelles of styrene maleic acid (SMA)-conjugated WIN were synthesized to reduce side-effects and increase drug efficacy. SMA-WIN micelles were characterised and their in vitro cytotoxic effect was compared to that of free WIN against triple-negative breast cancer (MDA-MB-231), hormone receptor-positive breast cancer (MCF-7) and castration-resistant prostate cancer (PC3) cell lines. SMA-WIN micelles were synthesised with a ~15% loading, 132.7 nm average diameter, -0.0388 mV charge, and pH-dependent release rate. A dose-dependent inhibition of cell growth was observed in all three cell lines treated with both free and micellar WIN, with both formulations demonstrating equal cytotoxicity.
  
  
  CONCLUSIONS
  SMA-WIN demonstrated characteristics theorized to improve in vivo drug biodistribution. Potent cytotoxicity was found against breast and prostate cancer cells in vitro, showing promise as a novel treatment against breast and prostate cancer.
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Susan
authors.initials: S
authors.lastname: Xian
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Neha N
authors.initials: NN
authors.lastname: Parayath
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Hayley
authors.initials: H
authors.lastname: Nehoff
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
authors.forename: Niroshini M
authors.initials: NM
authors.lastname: Giles
authors.affiliation: Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand khaled.greish@otago.ac.nz.
authors.forename: Khaled
authors.initials: K
authors.lastname: Greish
mesh_terms: D048588:Benzoxazines / Q000627:therapeutic use* / Q000633:toxicity; D002186:Cannabinoids / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008298:Maleates / Q000737:chemistry* / Q000633:toxicity; D008823:Micelles; D009025:Morpholines / Q000627:therapeutic use* / Q000633:toxicity; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D009281:Naphthalenes / Q000627:therapeutic use* / Q000633:toxicity; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D012015:Reference Standards; D055672:Static Electricity; D020058:Styrene / Q000737:chemistry* / Q000633:toxicity
chemical_list: D048588:Benzoxazines; D002186:Cannabinoids; D008298:Maleates; D008823:Micelles; D009025:Morpholines; D009281:Naphthalenes; D020058:Styrene; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C030272:maleic acid
keywords: Cannabinoids; WIN55,212-2; breast; cancer; micelle(s); nano-micelle; nanoparticle(s)