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

Authors Zhou H, Wei J, Dai Q, Wang L, Luo J, Cheang T, Wang S

Received 26 August 2014

Accepted for publication 13 December 2014

Published 1 July 2015 Volume 2015:10(1) Pages 4255—4266

DOI https://doi.org/10.2147/IJN.S73269

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Thomas J Webster

Hongyan Zhou,1,* Jinhuan Wei,2,* Qiangsheng Dai,3 Liping Wang,4 Junhang Luo,2 Tuckyun Cheang,4 Shenming Wang4

1Department of Neurological Intensive Care Unit, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Breast Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

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.
Conclusion: ACC/CaIP6 nanoparticles are a safe and efficient method of delivering siRNA for gene therapy in breast cancer.

Keywords: breast cancer, gene therapy, nanoparticles, small interfering RNA

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