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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2015
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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 |
Sumario: | 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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