title: Physicochemical characteristics and preliminary in vivo biological evaluation of nanocapsules loaded with siRNA targeting estrogen receptor alpha.
abstract: Specific siRNAs that target estrogen receptor alpha (ERalpha) were encapsulated in nanocapsules (NCs). We produced small (approximately 100-200 nm) ERalpha-siRNA NCs with a water core by incorporating two mixed duplexes of specific ERalpha-siRNAs (ERalpha-mix-siRNA) into NCs. The encapsulation yield that was obtained with poly(iso-butylcyanoacrylate) (PIBCA) NCs was low, whereas no release of trapped siRNA was observed for poly(ethylene)glycol-poly(D,L-lactide-co-glycolide) (PEG-PLGA) NCs. High levels of ERalpha-siRNA incorporation into PEG-epsilon-caprolactone-malic acid (PEG-PCL/MA) NCs (3.3 microM in a polymer solution at 16 mg/mL) were observed (72% yield). No difference in size or zeta potential was observed between siRNA NCs that were based on PEG-PCL/MA and empty NCs. Fluorescence quenching assays confirmed the incorporation of siRNA into the NC core. A persistent loss of ERalpha (90% over 5 days) was observed in MCF-7 human breast cancer cells that were exposed to PEG-PCL/MA NCs that were loaded with ERalpha-siRNA. The intravenous injection of these NCs into estradiol-stimulated MCF-7 cell xenografts led to a significant decrease in tumor growth and a decrease in ERalpha expression in tumor cells. These data indicate that a novel strategy, based on ERalpha-siRNA delivery, could be developed for the treatment of hormone-dependent breast cancers.
authors.affiliation: Physico-Chimie, Pharmacotechnie, Biopharmacie, Université Paris-Sud, CNRS UMR 8612 and IFR 141, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bouclier
authors.forename: Laurence
authors.initials: L
authors.lastname: Moine
authors.forename: Hervé
authors.initials: H
authors.lastname: Hillaireau
authors.forename: Véronique
authors.initials: V
authors.lastname: Marsaud
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Connault
authors.forename: Paule
authors.initials: P
authors.lastname: Opolon
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
authors.forename: Jack-Michel
authors.initials: JM
authors.lastname: Renoir
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D045744:Cell Line, Tumor; D002627:Chemistry, Physical / Q000379:methods*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D004655:Emulsions; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D006801:Humans; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D053769:Nanocapsules / Q000737:chemistry; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D004655:Emulsions; D047628:Estrogen Receptor alpha; D053769:Nanocapsules; D034741:RNA, Small Interfering