Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes

Wendian Zhang,1 Fangqi Peng,1 Taotao Zhou,1 Yifei Huang,2 Li Zhang,3 Peng Ye,4 Miao Lu,1 Guang Yang,5 Yongkang Gai,1 Tan Yang,1 Xiang Ma,1 Guangya Xiang1 1School of Pharmacy, Tongji Medical College, 2Department of Pharmacy, 3Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong...

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Autores principales:	Zhang W, Peng F, Zhou T, Huang Y, Zhang L, Ye P, Lu M, Yang G, Gai Y, Yang T, Ma X, Xiang G
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0c88d243534e48bb97c817ac9b817548
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spelling	oai:doaj.org-article:0c88d243534e48bb97c817ac9b8175482021-12-02T06:33:28ZTargeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes1178-2013https://doaj.org/article/0c88d243534e48bb97c817ac9b8175482015-07-01T00:00:00Zhttp://www.dovepress.com/targeted-delivery-of-chemically-modified-anti-mir-221-to-hepatocellula-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wendian Zhang,1 Fangqi Peng,1 Taotao Zhou,1 Yifei Huang,2 Li Zhang,3 Peng Ye,4 Miao Lu,1 Guang Yang,5 Yongkang Gai,1 Tan Yang,1 Xiang Ma,1 Guangya Xiang1 1School of Pharmacy, Tongji Medical College, 2Department of Pharmacy, 3Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 4Department of Pharmacy, Wuhan University, Renmin Hospital, 5School of Medicine, Jianghan University, Wuhan, People’s Republic of China Abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Gene therapy was established as a new strategy for treating HCC. To explore the potential delivery system to support the gene therapy of HCC, negatively charged liposomal delivery system was used to deliver miR-221 antisense oligonucleotide (anti-miR-221) to the transferrin (Tf) receptor over expressed HepG2 cells. The liposome exhibited a mean particle size of 122.5 nm, zeta potential of -15.74 mV, anti-miR-221 encapsulation efficiency of 70%, and excellent colloidal stability at 4°C. Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro. Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27kip1, and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome. After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27kip1, and TIMP3. Our results demonstrate that the Tf-targeted negatively charged liposome could be a potential therapeutic modality in the gene therapy of human HCC. Keywords: transferrin, gene, HCC, target delivery system, anionic liposome Zhang WPeng FZhou THuang YZhang LYe PLu MYang GGai YYang TMa XXiang GDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 4825-4836 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zhang W Peng F Zhou T Huang Y Zhang L Ye P Lu M Yang G Gai Y Yang T Ma X Xiang G Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes
description	Wendian Zhang,1 Fangqi Peng,1 Taotao Zhou,1 Yifei Huang,2 Li Zhang,3 Peng Ye,4 Miao Lu,1 Guang Yang,5 Yongkang Gai,1 Tan Yang,1 Xiang Ma,1 Guangya Xiang1 1School of Pharmacy, Tongji Medical College, 2Department of Pharmacy, 3Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 4Department of Pharmacy, Wuhan University, Renmin Hospital, 5School of Medicine, Jianghan University, Wuhan, People’s Republic of China Abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Gene therapy was established as a new strategy for treating HCC. To explore the potential delivery system to support the gene therapy of HCC, negatively charged liposomal delivery system was used to deliver miR-221 antisense oligonucleotide (anti-miR-221) to the transferrin (Tf) receptor over expressed HepG2 cells. The liposome exhibited a mean particle size of 122.5 nm, zeta potential of -15.74 mV, anti-miR-221 encapsulation efficiency of 70%, and excellent colloidal stability at 4°C. Anti-miR-221-encapsulated Tf-targeted liposome demonstrated a 15-fold higher delivery efficiency compared to nontargeted liposome in HepG2 cells in vitro. Anti-miR-221 Tf-targeted liposome effectively delivered anti-miR-221 to HepG2 cells, upregulated miR-221 target genes PTEN, P27kip1, and TIMP3, and exhibited greater silencing efficiency over nontargeted anti-miR-221 liposome. After intravenous injection into HepG2 tumor-bearing xenografted mice with Cy3-labeled anti-miR-221 Tf-targeted liposome, Cy3-anti-miR-221 was successfully delivered to the tumor site and increased the expressions of PTEN, P27kip1, and TIMP3. Our results demonstrate that the Tf-targeted negatively charged liposome could be a potential therapeutic modality in the gene therapy of human HCC. Keywords: transferrin, gene, HCC, target delivery system, anionic liposome
format	article
author	Zhang W Peng F Zhou T Huang Y Zhang L Ye P Lu M Yang G Gai Y Yang T Ma X Xiang G
author_facet	Zhang W Peng F Zhou T Huang Y Zhang L Ye P Lu M Yang G Gai Y Yang T Ma X Xiang G
author_sort	Zhang W
title	Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes
title_short	Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes
title_full	Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes
title_fullStr	Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes
title_full_unstemmed	Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes
title_sort	targeted delivery of chemically modified anti-mir-221 to hepatocellular carcinoma with negatively charged liposomes
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/0c88d243534e48bb97c817ac9b817548
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Targeted delivery of chemically modified anti-miR-221 to hepatocellular carcinoma with negatively charged liposomes

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