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Combination of PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma

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 Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles (MZF-NPs) under an...

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Autores principales: Tang, Qiusha, Lu, Mudan, Chen, Daozhen, Liu, Peidang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655962/
https://www.ncbi.nlm.nih.gov/pubmed/26604760
http://dx.doi.org/10.2147/IJN.S92179
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author Tang, Qiusha
Lu, Mudan
Chen, Daozhen
Liu, Peidang
author_facet Tang, Qiusha
Lu, Mudan
Chen, Daozhen
Liu, Peidang
author_sort Tang, Qiusha
collection PubMed
description 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 Mn(0.5)Zn(0.5)Fe(2)O(4) 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.
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spelling pubmed-46559622015-11-24 Combination of PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma Tang, Qiusha Lu, Mudan Chen, Daozhen Liu, Peidang Int J Nanomedicine Original Research 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 Mn(0.5)Zn(0.5)Fe(2)O(4) 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. Dove Medical Press 2015-11-18 /pmc/articles/PMC4655962/ /pubmed/26604760 http://dx.doi.org/10.2147/IJN.S92179 Text en © 2015 Tang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Tang, Qiusha
Lu, Mudan
Chen, Daozhen
Liu, Peidang
Combination of PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title Combination of PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_full Combination of PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_fullStr Combination of PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_full_unstemmed Combination of PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_short Combination of PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles and pHsp 70-HSV-TK/GCV with magnet-induced heating for treatment of hepatoma
title_sort combination of pei-mn(0.5)zn(0.5)fe(2)o(4) nanoparticles and phsp 70-hsv-tk/gcv with magnet-induced heating for treatment of hepatoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655962/
https://www.ncbi.nlm.nih.gov/pubmed/26604760
http://dx.doi.org/10.2147/IJN.S92179
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