The Use of Styrene Maleic Acid Nanomicelles Encapsulating the Synthetic Cannabinoid Analog WIN55,212-2 for the Treatment of Cancer

Anticancer Res. 2015 Sep;35(9):4707-12.

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.

Conclusion: 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.

Keywords: Cannabinoids; WIN55,212-2; breast; cancer; micelle(s); nano-micelle; nanoparticle(s).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzoxazines / therapeutic use*
  • Benzoxazines / toxicity
  • Cannabinoids / metabolism*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Humans
  • Inhibitory Concentration 50
  • Maleates / chemistry*
  • Maleates / toxicity
  • Micelles*
  • Morpholines / therapeutic use*
  • Morpholines / toxicity
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Naphthalenes / therapeutic use*
  • Naphthalenes / toxicity
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Particle Size
  • Reference Standards
  • Static Electricity
  • Styrene / chemistry*
  • Styrene / toxicity

Substances

  • Benzoxazines
  • Cannabinoids
  • Maleates
  • Micelles
  • Morpholines
  • Naphthalenes
  • Styrene
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • maleic acid