CaCO₃/CaIP₆ composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth

• Published in: International journal of nanomedicine 2015-07, Vol.10 (default), p.4255-4266
• Main Authors: Zhou, Hongyan, Wei, Jinhuan, Dai, Qiangsheng, Wang, Liping, Luo, Junhang, Cheang, Tuckyun, Wang, Shenming
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; breast cancer; Breast Neoplasms - chemistry; Calcium Carbonate - chemistry; Cell Proliferation - drug effects; gene therapy; Humans; Inositol Phosphates - chemistry; MCF-7 Cells; Mice; Nanocomposites - chemistry; nanoparticles; Original Research; Proto-Oncogene Proteins c-akt - genetics; RNA, Small Interfering - genetics; RNA, Small Interfering - pharmacokinetics; RNA, Small Interfering - pharmacology; small interfering RNA; Xenograft Model Antitumor Assays
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S73269

Small interfering RNA (siRNA)-mediated gene therapy is a promising strategy to temporarily inhibit the expression of genes involved in development of breast cancer. The lack of a safe and efficient gene delivery system has become a major hurdle for siRNA-mediated gene therapy in breast cancer. Our previous studies have demonstrated that inorganic amorphous calcium carbonate (ACC) hybrid nanospheres functionalized with CaIP6 (ACC/CaIP6) nanoparticles are an efficient nucleic acid delivery tool. The present study aimed to evaluate the safety and efficiency of ACC/CaIP6 in delivering siRNA targeting AKT1 (siAKT1) for the treatment of breast cancer. The cytotoxicity of the ACC/CaIP6 nanoparticles was evaluated using a tetrazolium assay. The transfection efficiency and intracellular distribution of ACC/siAKT1 were analyzed by flow cytometry and confocal laser scanning microscopy, respectively. A series of in vitro and in vivo assays was performed to evaluate the effects of ACC/CaIP6/siAKT1 on growth of breast cancer cells. ACC/CaIP6 nanoparticles effectively transfected cells with little or no toxicity. AKT1 knockdown by ACC/CaIP6/siAKT1 inhibited cell cycle progression and promoted apoptosis of MCF-7 cells. Intratumoral injection of ACC/CaIP6/siAKT1 significantly suppressed the growth of breast cancer in mice. ACC/CaIP6 nanoparticles are a safe and efficient method of delivering siRNA for gene therapy in breast cancer.