Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma

Qiusha Tang,1 Mudan Lu,2 Daozhen Chen,2 Peidang Liu1 1School of Medicine, Southeast University, Nanjing, 2Genetic Laboratory, Wuxi Hospital for Maternal and Child Health Care, the Affiliated Hospital of Nanjing Medical University, Wuxi, People’s Republic of China Background: To...

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Autores principales:	Tang QS, Lu MD, Chen DZ, Liu PD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/faa33a843aaf487491f4a54d04c97831
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spelling	oai:doaj.org-article:faa33a843aaf487491f4a54d04c978312021-12-02T00:40:15ZCombination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma1178-2013https://doaj.org/article/faa33a843aaf487491f4a54d04c978312015-11-01T00:00:00Zhttps://www.dovepress.com/combination-of-pei-mn05zn05fe2o4-nanoparticles-and-phsp-70-hsv-tkgcv-w-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Qiusha Tang,1 Mudan Lu,2 Daozhen Chen,2 Peidang Liu1 1School of Medicine, Southeast University, Nanjing, 2Genetic Laboratory, Wuxi Hospital for Maternal and Child Health Care, the Affiliated Hospital of Nanjing Medical University, Wuxi, People’s Republic of China Background: To explore a new combination of thermal treatment and gene therapy for hepatoma, a heat-inducible herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy system was developed in which thermal energy generated by Mn0.5Zn0.5Fe2O4 nanoparticles (MZF-NPs) under an alternating magnetic field was used to activate gene expression.Methods: First, a recombinant eukaryotic plasmid, pHsp 70-HSV-TK, was constructed as a target gene for therapy. This recombinant plasmid was used to transfect SMMC-7721 hepatoma cells and the gene expression was evaluated. Magnet-induced heating was then applied to cells to assess the antihepatoma effects of the polyethylenimine (PEI)-MZF-NPs/pHsp 70-HSV-TK/GCV complex, in vitro and in vivo.Results: The results showed that cells were successfully transfected with pHsp 70-HSV-TK and that expression levels of HSV-TK remained stable. Both in vitro and in vivo results indicated that the combination of gene therapy and heat treatment resulted in better therapeutic effects than heating-alone group. The rates of apoptosis and necrosis in the combined treatment group were 49.0% and 7.21%, respectively. The rate of inhibition of cell proliferation in the combined treatment group was significantly higher (87.5%) than that in the heating-alone group (65.8%; P<0.01). The tumor volume and mass inhibition rates of the combined treatment group were 91.3% and 87.91%, respectively, and were significantly higher than the corresponding rates of the heating-alone group (70.41% and 57.14%; P<0.01). The expression levels of Stat3 and Bcl-xL messenger RNA and p-Stat3 and Bcl-xL protein in the combined treatment group were significantly lower than those in the other groups (P<0.01). The expression levels of Bax messenger RNA and protein in the recombinant plasmid group were significantly higher than those in the other groups (P<0.01).Conclusion: It can therefore be concluded that the combined application of heat treatment and gene therapy has a synergistic and complementary effect and that PEI-MZF-NPs can simultaneously act both as a nonviral gene vector and a magnet-induced source of heat, thereby representing a viable approach for the treatment of cancer. Keywords: Mn0.5Zn0.5Fe2O4 nanoparticles, heat-inducible gene expression, hyperthermia, gene therapy, HSV-TK/GCV, SMMC-7721 hepatoma cellsTang QSLu MDChen DZLiu PDDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 7129-7143 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Tang QS Lu MD Chen DZ Liu PD Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
description	Qiusha Tang,1 Mudan Lu,2 Daozhen Chen,2 Peidang Liu1 1School of Medicine, Southeast University, Nanjing, 2Genetic Laboratory, Wuxi Hospital for Maternal and Child Health Care, the Affiliated Hospital of Nanjing Medical University, Wuxi, People’s Republic of China Background: To explore a new combination of thermal treatment and gene therapy for hepatoma, a heat-inducible herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy system was developed in which thermal energy generated by Mn0.5Zn0.5Fe2O4 nanoparticles (MZF-NPs) under an alternating magnetic field was used to activate gene expression.Methods: First, a recombinant eukaryotic plasmid, pHsp 70-HSV-TK, was constructed as a target gene for therapy. This recombinant plasmid was used to transfect SMMC-7721 hepatoma cells and the gene expression was evaluated. Magnet-induced heating was then applied to cells to assess the antihepatoma effects of the polyethylenimine (PEI)-MZF-NPs/pHsp 70-HSV-TK/GCV complex, in vitro and in vivo.Results: The results showed that cells were successfully transfected with pHsp 70-HSV-TK and that expression levels of HSV-TK remained stable. Both in vitro and in vivo results indicated that the combination of gene therapy and heat treatment resulted in better therapeutic effects than heating-alone group. The rates of apoptosis and necrosis in the combined treatment group were 49.0% and 7.21%, respectively. The rate of inhibition of cell proliferation in the combined treatment group was significantly higher (87.5%) than that in the heating-alone group (65.8%; P<0.01). The tumor volume and mass inhibition rates of the combined treatment group were 91.3% and 87.91%, respectively, and were significantly higher than the corresponding rates of the heating-alone group (70.41% and 57.14%; P<0.01). The expression levels of Stat3 and Bcl-xL messenger RNA and p-Stat3 and Bcl-xL protein in the combined treatment group were significantly lower than those in the other groups (P<0.01). The expression levels of Bax messenger RNA and protein in the recombinant plasmid group were significantly higher than those in the other groups (P<0.01).Conclusion: It can therefore be concluded that the combined application of heat treatment and gene therapy has a synergistic and complementary effect and that PEI-MZF-NPs can simultaneously act both as a nonviral gene vector and a magnet-induced source of heat, thereby representing a viable approach for the treatment of cancer. Keywords: Mn0.5Zn0.5Fe2O4 nanoparticles, heat-inducible gene expression, hyperthermia, gene therapy, HSV-TK/GCV, SMMC-7721 hepatoma cells
format	article
author	Tang QS Lu MD Chen DZ Liu PD
author_facet	Tang QS Lu MD Chen DZ Liu PD
author_sort	Tang QS
title	Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_short	Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_full	Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_fullStr	Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_full_unstemmed	Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_sort	combination of pei-mn0.5zn0.5fe2o4 nanoparticles and phsp 70-hsv-tk/gcv with magnet-induced heating for treatment of hepatoma
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/faa33a843aaf487491f4a54d04c97831
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Combination of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma

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