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

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...

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Autores principales:	Zhou H, Wei J, Dai Q, Wang L, Luo J, Cheang T, Wang S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/9eef9805bedd48e8924078bc86ff4244
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spelling	oai:doaj.org-article:9eef9805bedd48e8924078bc86ff42442021-12-02T06:46:22ZCaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth1178-2013https://doaj.org/article/9eef9805bedd48e8924078bc86ff42442015-07-01T00:00:00Zhttp://www.dovepress.com/caco3caip6-composite-nanoparticles-effectively-deliver-akt1-small-inte-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hongyan 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 RNAZhou HWei JDai QWang LLuo JCheang TWang SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 4255-4266 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhou H Wei J Dai Q Wang L Luo J Cheang T Wang S CaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth
description	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
format	article
author	Zhou H Wei J Dai Q Wang L Luo J Cheang T Wang S
author_facet	Zhou H Wei J Dai Q Wang L Luo J Cheang T Wang S
author_sort	Zhou H
title	CaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth
title_short	CaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth
title_full	CaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth
title_fullStr	CaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth
title_full_unstemmed	CaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth
title_sort	caco3/caip6 composite nanoparticles effectively deliver akt1 small interfering rna to inhibit human breast cancer growth
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/9eef9805bedd48e8924078bc86ff4244
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_version_	1718399769084166144

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

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