Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy

Jun-Yi Wu,1,* Zhong-Xia Wang,1,* Guang Zhang,1 Xian Lu,1 Guang-Hui Qiang,2 Wei Hu,2 An-Lai Ji,3 Jun-Hua Wu,4 Chun-Ping Jiang1 1Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China; 2Department of Hepatobiliary Surgery, Dru...

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Autores principales:	Wu JY, Wang ZX, Zhang G, Lu X, Qiang GH, Hu W, Ji AL, Wu JH, Jiang CP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	LCP-II NPs autophagy FTY720 Beclin 1 co-delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2af20381a7c94907ab21a41677cfbd8a
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spelling	oai:doaj.org-article:2af20381a7c94907ab21a41677cfbd8a2021-12-02T05:09:48ZTargeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy1178-2013https://doaj.org/article/2af20381a7c94907ab21a41677cfbd8a2018-03-01T00:00:00Zhttps://www.dovepress.com/targeted-co-delivery-of-beclin-1-sirna-and-fty720-to-hepatocellular-ca-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jun-Yi Wu,1,* Zhong-Xia Wang,1,* Guang Zhang,1 Xian Lu,1 Guang-Hui Qiang,2 Wei Hu,2 An-Lai Ji,3 Jun-Hua Wu,4 Chun-Ping Jiang1 1Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China; 2Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China; 3Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; 4Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China *These authors contributed equally to this work Purpose: FTY720, known as fingolimod, is a new immunosuppressive agent with effective anticancer properties. Although it was recently confirmed that FTY720 inhibits cancer cell proliferation, FTY720 can also induce protective autophagy and reduce cytotoxicity. Blocking autophagy with Beclin 1 siRNA after treatment with FTY720 promotes apoptosis. The objective of this study was to enhance the anticancer effect of FTY720 in hepatocellular carcinoma (HCC) by targeted co-delivery of FTY720 and Beclin 1 siRNA using calcium phosphate (CaP) nanoparticles (NPs).Materials and methods: First, the siRNA was encapsulated within the CaP core. To form an asymmetric lipid bilayer structure, we then used an anionic lipid for the inner leaflet and a cationic lipid for the outer leaflet; after removing chloroform by rotary evaporation, these lipids were dispersed in a saline solution with FTY720. The NPs were analyzed by transmission electron microscopy, dynamic light scattering and ultraviolet–visible spectrophotometry. Cancer cell viability and cell death were analyzed by MTT assays, fluorescence-activated cell sorting analysis and Western blotting. In addition, the in vivo effects of the NPs were investigated using an athymic nude mouse subcutaneous transplantation tumor model.Results: When the CaP NPs, called LCP-II NPs, were loaded with FTY720 and siRNA, they exhibited the expected size and were internalized by cells. These NPs were stable in systemic circulation. Furthermore, co-delivery of FTY720 and Beclin 1 siRNA significantly increased cytotoxicity in vitro and in vivo compared with that caused by treatment with the free drug alone.Conclusion: The CaP NP system can be further developed for co-delivery of FTY720 and Beclin 1 siRNA to treat HCC, enhancing the anticancer efficacy of FTY720. Our findings provide a new insight into HCC treatment with co-delivered small molecules and siRNA, and these results can be readily translated into cancer clinical trials. Keywords: LCP-II NPs, autophagy, FTY720, Beclin 1, co-delivery Wu JYWang ZXZhang GLu XQiang GHHu WJi ALWu JHJiang CPDove Medical PressarticleLCP-II NPsautophagyFTY720Beclin 1co-deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1265-1280 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	LCP-II NPs autophagy FTY720 Beclin 1 co-delivery Medicine (General) R5-920
spellingShingle	LCP-II NPs autophagy FTY720 Beclin 1 co-delivery Medicine (General) R5-920 Wu JY Wang ZX Zhang G Lu X Qiang GH Hu W Ji AL Wu JH Jiang CP Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy
description	Jun-Yi Wu,1,* Zhong-Xia Wang,1,* Guang Zhang,1 Xian Lu,1 Guang-Hui Qiang,2 Wei Hu,2 An-Lai Ji,3 Jun-Hua Wu,4 Chun-Ping Jiang1 1Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China; 2Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China; 3Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; 4Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China *These authors contributed equally to this work Purpose: FTY720, known as fingolimod, is a new immunosuppressive agent with effective anticancer properties. Although it was recently confirmed that FTY720 inhibits cancer cell proliferation, FTY720 can also induce protective autophagy and reduce cytotoxicity. Blocking autophagy with Beclin 1 siRNA after treatment with FTY720 promotes apoptosis. The objective of this study was to enhance the anticancer effect of FTY720 in hepatocellular carcinoma (HCC) by targeted co-delivery of FTY720 and Beclin 1 siRNA using calcium phosphate (CaP) nanoparticles (NPs).Materials and methods: First, the siRNA was encapsulated within the CaP core. To form an asymmetric lipid bilayer structure, we then used an anionic lipid for the inner leaflet and a cationic lipid for the outer leaflet; after removing chloroform by rotary evaporation, these lipids were dispersed in a saline solution with FTY720. The NPs were analyzed by transmission electron microscopy, dynamic light scattering and ultraviolet–visible spectrophotometry. Cancer cell viability and cell death were analyzed by MTT assays, fluorescence-activated cell sorting analysis and Western blotting. In addition, the in vivo effects of the NPs were investigated using an athymic nude mouse subcutaneous transplantation tumor model.Results: When the CaP NPs, called LCP-II NPs, were loaded with FTY720 and siRNA, they exhibited the expected size and were internalized by cells. These NPs were stable in systemic circulation. Furthermore, co-delivery of FTY720 and Beclin 1 siRNA significantly increased cytotoxicity in vitro and in vivo compared with that caused by treatment with the free drug alone.Conclusion: The CaP NP system can be further developed for co-delivery of FTY720 and Beclin 1 siRNA to treat HCC, enhancing the anticancer efficacy of FTY720. Our findings provide a new insight into HCC treatment with co-delivered small molecules and siRNA, and these results can be readily translated into cancer clinical trials. Keywords: LCP-II NPs, autophagy, FTY720, Beclin 1, co-delivery
format	article
author	Wu JY Wang ZX Zhang G Lu X Qiang GH Hu W Ji AL Wu JH Jiang CP
author_facet	Wu JY Wang ZX Zhang G Lu X Qiang GH Hu W Ji AL Wu JH Jiang CP
author_sort	Wu JY
title	Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy
title_short	Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy
title_full	Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy
title_fullStr	Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy
title_full_unstemmed	Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy
title_sort	targeted co-delivery of beclin 1 sirna and fty720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/2af20381a7c94907ab21a41677cfbd8a
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Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy

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