Physicochemical Characteristics and Preliminary in Vivo Biological Evaluation of Nanocapsules Loaded with siRNA Targeting Estrogen Receptor Alpha

• Published in: Biomacromolecules 2008-10, Vol.9 (10), p.2881-2890
• Main Authors: Bouclier, Céline, Moine, Laurence, Hillaireau, Hervé, Marsaud, Véronique, Connault, Elisabeth, Opolon, Paule, Couvreur, Patrick, Fattal, Elias, Renoir, Jack-Michel
• Format: Article
• Language: English
• Subjects: Animals; Applied sciences; Biocompatible Materials - chemistry; Biological and medical sciences; Cell Line, Tumor; Chemistry, Physical - methods; Drug Delivery Systems; Drug Screening Assays, Antitumor; Emulsions; Estrogen Receptor alpha - metabolism; Exact sciences and technology; Female; Forms of application and semi-finished materials; General pharmacology; Humans; Materials Testing; Medical sciences; Mice; Mice, Nude; Miscellaneous; Nanocapsules - chemistry; Neoplasm Transplantation; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymer industry, paints, wood; RNA, Small Interfering - metabolism; Technology of polymers
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm800664c

Specific siRNAs that target estrogen receptor alpha (ERα) were encapsulated in nanocapsules (NCs). We produced small (∼100−200 nm) ERα−siRNA NCs with a water core by incorporating two mixed duplexes of specific ERα−siRNAs (ERα−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 ERα−siRNA incorporation into PEG-ε-caprolactone-malic acid (PEG−PCL/MA) NCs (3.3 μM 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 ERα (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 ERα−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 ERα expression in tumor cells. These data indicate that a novel strategy, based on ERα−siRNA delivery, could be developed for the treatment of hormone-dependent breast cancers.