Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells

Jing Qu,1 Weiwei Wang,1 Yanfei Feng,1 Longxing Niu,1 Mingzhong Li,1 Jicheng Yang,2 Yufeng Xie3 1National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, People′s Republic of China; 2Cell and Molecular Biology Institute...

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Autores principales:	Qu J, Wang W, Feng Y, Niu L, Li M, Yang J, Xie Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	silk fibroin adenovirus cationic modification hepatoma carcinoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b4b22b4bd4a1433eba2c886febc6b0d1
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spelling	oai:doaj.org-article:b4b22b4bd4a1433eba2c886febc6b0d12021-12-02T03:23:53ZCationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells1178-2013https://doaj.org/article/b4b22b4bd4a1433eba2c886febc6b0d12019-12-01T00:00:00Zhttps://www.dovepress.com/cationic-antheraea-pernyi-silk-fibroin-modified-adenovirus-mediated-in-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jing Qu,1 Weiwei Wang,1 Yanfei Feng,1 Longxing Niu,1 Mingzhong Li,1 Jicheng Yang,2 Yufeng Xie3 1National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, People′s Republic of China; 2Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou 215123, People′s Republic of China; 3Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, People′s Republic of ChinaCorrespondence: Mingzhong LiNational Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, No. 199 Ren’ai Road, Suzhou 215123, People’s Republic of ChinaTel +86-512-6706-1150Fax +86-512-6724-6786Email mzli@suda.edu.cnYufeng XieDepartment of Oncology, First Affiliated Hospital of Soochow University, No.188 Shizi Road, Suzhou 215006, People′s Republic of ChinaTel +86-512-6778-0645Email sdxyf@163.comIntroduction: Cancer gene therapy requires both effective tumor suppressor genes and safe vectors that express target genes efficiently. Inhibitor of growth 4 (ING4) inhibits tumor growth via multiple pathways. Interleukin-24 (IL-24) also has tumor-suppressive activity against a broad spectrum of human cancers. Adenovirus (Ad) vectors exhibit high infection efficiency, but potential toxicity related to high doses of adenovirus has led to careful reconsideration of their use in human clinical trials. Antheraea pernyi silk fibroin (ASF) is a cytocompatible and biodegradable natural polymer, and it possesses Arg–Gly–Asp sequences exhibiting a high binding affinity and selectivity for αvβ3 and αvβ5 integrin receptors, which are overexpressed in tumor vessels and most tumor cells.Methods: In this study, an Arg-Gly-Asp peptide-modified Ad vector coexpressing ING4 and IL-24 was constructed by homologous recombination of the dual gene coexpression transfer plasmid and RGD-modified pAdEasy-1 adenoviral backbone plasmid. The cationic ASF (CASF) was prepared by modifying ASF with low-molecular-weight PEI. The negatively charged Ad vector was modified with CASF to form a CASF/Ad complex.Results: Human hepatoma carcinoma SMMC-7721 cells and normal hepatic L-02 cells were infected with the CASF/Ad complex, which showed significantly higher infection efficiency than the naked Ad. The CASF/Ad complex could effectively mediate the expression of the target gene ING4 in SMMC-7721 cells and the secretion of the target gene IL-24 from SMMC-7721 cells, thus inducing apoptosis of hepatoma carcinoma SMMC-7721 cells. The viability of SMMC-7721 and L-02 cells infected with the CASF/Ad complex was further assessed, and it was found that the growth of SMMC-7721 cells was significantly inhibited but that the growth and proliferation of L-02 cells were not affected.Conclusion: The CASF/Ad complex constructed in this study, showing improved infection efficiency and enhanced suppressive effects on human hepatoma carcinoma SMMC-7721 cells, has the potential to reduce the dose of adenovirus and still maintain high infection efficiency and tumor inhibition.Keywords: silk fibroin, adenovirus, cationic modification, hepatoma carcinomaQu JWang WFeng YNiu LLi MYang JXie YDove Medical Pressarticlesilk fibroinadenoviruscationic modificationhepatoma carcinomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 9745-9761 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	silk fibroin adenovirus cationic modification hepatoma carcinoma Medicine (General) R5-920
spellingShingle	silk fibroin adenovirus cationic modification hepatoma carcinoma Medicine (General) R5-920 Qu J Wang W Feng Y Niu L Li M Yang J Xie Y Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells
description	Jing Qu,1 Weiwei Wang,1 Yanfei Feng,1 Longxing Niu,1 Mingzhong Li,1 Jicheng Yang,2 Yufeng Xie3 1National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, Suzhou 215123, People′s Republic of China; 2Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou 215123, People′s Republic of China; 3Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou 215006, People′s Republic of ChinaCorrespondence: Mingzhong LiNational Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering, Soochow University, No. 199 Ren’ai Road, Suzhou 215123, People’s Republic of ChinaTel +86-512-6706-1150Fax +86-512-6724-6786Email mzli@suda.edu.cnYufeng XieDepartment of Oncology, First Affiliated Hospital of Soochow University, No.188 Shizi Road, Suzhou 215006, People′s Republic of ChinaTel +86-512-6778-0645Email sdxyf@163.comIntroduction: Cancer gene therapy requires both effective tumor suppressor genes and safe vectors that express target genes efficiently. Inhibitor of growth 4 (ING4) inhibits tumor growth via multiple pathways. Interleukin-24 (IL-24) also has tumor-suppressive activity against a broad spectrum of human cancers. Adenovirus (Ad) vectors exhibit high infection efficiency, but potential toxicity related to high doses of adenovirus has led to careful reconsideration of their use in human clinical trials. Antheraea pernyi silk fibroin (ASF) is a cytocompatible and biodegradable natural polymer, and it possesses Arg–Gly–Asp sequences exhibiting a high binding affinity and selectivity for αvβ3 and αvβ5 integrin receptors, which are overexpressed in tumor vessels and most tumor cells.Methods: In this study, an Arg-Gly-Asp peptide-modified Ad vector coexpressing ING4 and IL-24 was constructed by homologous recombination of the dual gene coexpression transfer plasmid and RGD-modified pAdEasy-1 adenoviral backbone plasmid. The cationic ASF (CASF) was prepared by modifying ASF with low-molecular-weight PEI. The negatively charged Ad vector was modified with CASF to form a CASF/Ad complex.Results: Human hepatoma carcinoma SMMC-7721 cells and normal hepatic L-02 cells were infected with the CASF/Ad complex, which showed significantly higher infection efficiency than the naked Ad. The CASF/Ad complex could effectively mediate the expression of the target gene ING4 in SMMC-7721 cells and the secretion of the target gene IL-24 from SMMC-7721 cells, thus inducing apoptosis of hepatoma carcinoma SMMC-7721 cells. The viability of SMMC-7721 and L-02 cells infected with the CASF/Ad complex was further assessed, and it was found that the growth of SMMC-7721 cells was significantly inhibited but that the growth and proliferation of L-02 cells were not affected.Conclusion: The CASF/Ad complex constructed in this study, showing improved infection efficiency and enhanced suppressive effects on human hepatoma carcinoma SMMC-7721 cells, has the potential to reduce the dose of adenovirus and still maintain high infection efficiency and tumor inhibition.Keywords: silk fibroin, adenovirus, cationic modification, hepatoma carcinoma
format	article
author	Qu J Wang W Feng Y Niu L Li M Yang J Xie Y
author_facet	Qu J Wang W Feng Y Niu L Li M Yang J Xie Y
author_sort	Qu J
title	Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells
title_short	Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells
title_full	Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells
title_fullStr	Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells
title_full_unstemmed	Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells
title_sort	cationic antheraea pernyi silk fibroin-modified adenovirus-mediated ing4 and il-24 dual gene coexpression vector suppresses the growth of hepatoma carcinoma cells
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/b4b22b4bd4a1433eba2c886febc6b0d1
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Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells

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