Physicochemical characteristics and preliminary in vivo biological evaluation of nanocapsules loaded with siRNA targeting estrogen receptor alpha.
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.
Bouclier
Céline
C
Physico-Chimie, Pharmacotechnie, Biopharmacie, Université Paris-Sud, CNRS UMR 8612 and IFR 141, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.
Moine
Laurence
L
Hillaireau
Hervé
H
Marsaud
Véronique
V
Connault
Elisabeth
E
Opolon
Paule
P
Couvreur
Patrick
P
Fattal
Elias
E
Renoir
Jack-Michel
JM
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*
D001672:Biocompatible Materials; D004655:Emulsions; D047628:Estrogen Receptor alpha; D053769:Nanocapsules; D034741:RNA, Small Interfering