title: Polymeric nanocapsules prevent oxidation of core-loaded molecules: evidence based on the effects of docosahexaenoic acid and neuroprostane on breast cancer cells proliferation.
abstract: BACKGROUND
  Nanocapsules, as a delivery system, are able to target drugs and other biologically sensitive molecules to specific cells or organs. This system has been intensively investigated as a way to protect bioactives drugs from inactivation upon interaction with the body and to ensure the release to the target. However, the mechanism of improved activity of the nanoencapsulated molecules is far from being understood at the cellular and subcellular levels. Epidemiological studies suggest that dietary polyunsaturated fatty acids (PUFA) can reduce the morbidity and mortality from breast cancer. This influence could be modulated by the oxidative status of the diet and it has been suggested that the anti-proliferative properties of docosahexaenoic acid (DHA) are enhanced by pro-oxidant agents.
  
  
  METHODS
  The effect of encapsulation of PUFA on breast cancer cell proliferation in different oxidative medium was evaluated in vitro. We compared the proliferation of the human breast cancer cell line MDA-MB-231 and of the non-cancer human mammary epithelial cell line MCF-10A in different experimental conditions.
  
  
  RESULTS
  DHA possessed anti-proliferative properties that were prevented by alpha-tocopherol (an antioxidant) and enhanced by the pro-oxidant hydrogen peroxide that confirms that DHA has to be oxidized to exert its anti-proliferative properties. We also evaluated the anti-proliferative effects of the 4(RS)-4-F4t-neuroprostane, a bioactive, non-enzymatic oxygenated metabolite of DHA known to play a major role in the prevention of cardiovascular diseases. DHA-loaded nanocapsules was less potent than non-encapsulated DHA while co-encapsulation of DHA with H2O2 maintained the inhibition of proliferation. The nanocapsules slightly improves the anti-proliferative effect in the case of 4(RS)-4-F4t-neuroprostane that is more hydrophilic than DHA.
  
  
  CONCLUSIONS
  Overall, our findings suggest that the sensitivity of tumor cell lines to DHA involves oxidized metabolites. They also indicate that neuroprostane is a metabolite participating in the growth reducing effect of DHA, but it is not the sole. These results also suggest that NC seek to enhance the stability against degradation, enhance cellular availability, and control the release of bioactive fatty acids following their lipophilicities.
authors.affiliation: Inserm U1046, UMR CNRS 9214, Physiologie et Médecine Expérimentale du Cœur et des, Muscles - PHYMEDEXP, Université de Montpellier, CHU Arnaud de Villeneuve, Bâtiment Crastes de Paulet, 371 avenue du doyen Gaston Giraud, 34295 Montpellier Cedex 5, Montpellier, France. jerome.roy@inserm.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Roy
authors.affiliation: Inserm U1046, UMR CNRS 9214, Physiologie et Médecine Expérimentale du Cœur et des, Muscles - PHYMEDEXP, Université de Montpellier, CHU Arnaud de Villeneuve, Bâtiment Crastes de Paulet, 371 avenue du doyen Gaston Giraud, 34295 Montpellier Cedex 5, Montpellier, France. liliamto@gmail.com.|Laboratório de Desenvolvimento Galênico e Nanotecnologia - CiPharma, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil. liliamto@gmail.com.
authors.forename: Liliam Teixeira
authors.initials: LT
authors.lastname: Oliveira
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Université de Montpellier, ENSCM, Montpellier, France. camille.oger@umontpellier.fr.
authors.forename: Camille
authors.initials: C
authors.lastname: Oger
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Université de Montpellier, ENSCM, Montpellier, France. jgalano@univ-montp1.fr.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Galano
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Université de Montpellier, ENSCM, Montpellier, France. valerie.bultel@univ-montp1.fr.
authors.forename: Valerie
authors.initials: V
authors.lastname: Bultel-Poncé
authors.affiliation: Inserm U1046, UMR CNRS 9214, Physiologie et Médecine Expérimentale du Cœur et des, Muscles - PHYMEDEXP, Université de Montpellier, CHU Arnaud de Villeneuve, Bâtiment Crastes de Paulet, 371 avenue du doyen Gaston Giraud, 34295 Montpellier Cedex 5, Montpellier, France. sylvain.richard@inserm.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Richard
authors.affiliation: Laboratório de Desenvolvimento Galênico e Nanotecnologia - CiPharma, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil. agguimar@gmail.com.
authors.forename: Andrea Grabe
authors.initials: AG
authors.lastname: Guimaraes
authors.affiliation: Centro Tecnológico CETEC SENAI/FIEMG-Belo Horizonte, Minas Gerais, Brazil. jvilela@fiemg.com.br.
authors.forename: José Mário Carneiro
authors.initials: JM
authors.lastname: Vilela
authors.affiliation: Centro Tecnológico CETEC SENAI/FIEMG-Belo Horizonte, Minas Gerais, Brazil. margareth.andrade@fiemg.com.br.
authors.forename: Margareth Spangler
authors.initials: MS
authors.lastname: Andrade
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), CNRS UMR 5247, Université de Montpellier, ENSCM, Montpellier, France. thierry.durand@umontpellier.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.affiliation: Inserm U1069, Nutrition, Croissance et Cancer, Université François-Rabelais de Tours, Tours, France. pierre.besson@univ-tours.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Besson
authors.affiliation: Laboratório de Desenvolvimento Galênico e Nanotecnologia - CiPharma, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais, Brazil. vamosqueira@gmail.com.
authors.forename: Vanessa Carla Furtado
authors.initials: VC
authors.lastname: Mosqueira
authors.affiliation: Inserm U1046, UMR CNRS 9214, Physiologie et Médecine Expérimentale du Cœur et des, Muscles - PHYMEDEXP, Université de Montpellier, CHU Arnaud de Villeneuve, Bâtiment Crastes de Paulet, 371 avenue du doyen Gaston Giraud, 34295 Montpellier Cedex 5, Montpellier, France. Jean-Yves.Le-Guennec@inserm.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Le Guennec
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry; D058632:Neuroprostanes / Q000008:administration & dosage* / Q000737:chemistry; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D053769:Nanocapsules; D058632:Neuroprostanes; D017382:Reactive Oxygen Species; D004281:Docosahexaenoic Acids; D006861:Hydrogen Peroxide