title: CaCO₃/CaIP₆ composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  ACC/CaIP6 nanoparticles are a safe and efficient method of delivering siRNA for gene therapy in breast cancer.
authors.affiliation: Department of Neurological Intensive Care Unit, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Qiangsheng
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Department of Breast Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Junhang
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Breast Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Tuckyun
authors.initials: T
authors.lastname: Cheang
authors.affiliation: Department of Breast Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Shenming
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001943:Breast Neoplasms / Q000737:chemistry; D002119:Calcium Carbonate / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007295:Inositol Phosphates / Q000737:chemistry*; D061986:MCF-7 Cells; D051379:Mice; D053761:Nanocomposites / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007295:Inositol Phosphates; D034741:RNA, Small Interfering; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D002119:Calcium Carbonate
keywords: breast cancer; gene therapy; nanoparticles; small interfering RNA