title: New core-shell nanoparticules for the intravenous delivery of siRNA to experimental thyroid papillary carcinoma.
abstract: OBJECTIVE
  Development of efficient in vivo delivery nanodevices remains a major challenge to achieve clinical application of siRNA. The present study refers to the conception of core-shell nanoparticles aiming to make possible intravenous administration of chemically unmodified siRNA oriented towards the junction oncogene of the papillary thyroid carcinoma.
  
  
  METHODS
  Nanoparticles were prepared by redox radical emulsion polymerization of isobutylcyanoacrylate and isohexylcyanoacrylate with chitosan. The loading of the nanoparticles with siRNA was achieved by adsorption. The biological activity of the siRNA-loaded nanoparticles was assessed on mice bearing a papillary thyroid carcinoma after intratumoral and intravenous administration.
  
  
  RESULTS
  Chitosan-coated nanoparticles with a diameter of 60 nm were obtained by adding 3% pluronic in the preparation medium. siRNA were associated with the nanoparticles by surface adsorption. In vivo, the antisense siRNA associated with the nanoparticles lead to a strong antitumoral activity. The tumor growth was almost stopped after intravenous injection of the antisense siRNA-loaded nanoparticles, while in all control experiments, the tumor size was increased by at least 10 times.
  
  
  CONCLUSIONS
  This work showed that poly(alkylcyanoacrylate) nanoparticles coated with chitosan are suitable carriers to achieve in vivo delivery of active siRNA to tumor including after systemic administration.
authors.affiliation: Université de Paris-Sud-11, UMR CNRS 8612, 5 rue J.B. Clément, 92296, Châtenay-Malabry, France.
authors.forename: Henri
authors.initials: H
authors.lastname: de Martimprey
authors.forename: Jean-Rémi
authors.initials: JR
authors.lastname: Bertrand
authors.forename: Claude
authors.initials: C
authors.lastname: Malvy
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Christine
authors.initials: C
authors.lastname: Vauthier
mesh_terms: D000818:Animals; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D034741:RNA, Small Interfering; D048271:Chitosan