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载聚乙烯亚胺-锰锌铁氧体纳米粒子/pEgr1-HSV-TK/GCV 的联合放射和磁致热疗对肝癌的治疗作用。

The therapeutic effect of PEI-Mn0.5Zn0.5Fe2O4 nanoparticles/pEgr1-HSV-TK/GCV associated with radiation and magnet-induced heating on hepatoma.

机构信息

Medical School of Southeast University, No. 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, China.

出版信息

Nanoscale. 2013 Feb 7;5(3):991-1000. doi: 10.1039/c2nr32930a. Epub 2012 Dec 18.

DOI:10.1039/c2nr32930a
PMID:23250046
Abstract

Comprehensive therapy based on the integration of hyperthermia, radiation, gene therapy and chemotherapy is a promising area of study in cancer treatment. Using PEI-Mn(0.5)Zn(0.5)Fe(2)O(4) nanoparticles (PEI-MZF-NPs) as a gene transfer vector, the authors transfected self-prepared pEgr1-HSV-TK into HepG2 cells and measured the expression of the exogenous gene HSV-TK by RT-PCR. The results showed that HSV-TK was successfully transfected into HepG2 cells and the expression levels of HSV-TK remained stable. Besides, PEI-MZF-NPs were used as magnetic media for thermotherapy to treat hepatoma by magnet-induced heating, combined with radiation-gene therapy. Both in vitro and in vivo results suggest that this combined treatment with gene, radiation and heating has a better therapeutic effect than any of them alone. The apoptotic rate and necrotic rate of the combined treatment group was 51.84% and 15.45%, respectively. In contrast, it was only 20.55% and 6.80% in the radiation-gene group, 7.49% and 3.62% in the radiation-alone group, 15.23% and 7.90% in the heating-alone group, and only 3.52% and 2.16% in the blank control group. The inhibition rate of cell proliferation (88.5%) of the combined treatment group was significantly higher than that of the radiation-gene group (59.5%), radiation-alone group (37.6%) and heating-alone group (60.6%). The tumor volume and mass inhibition rate of the combined treatment group was 94.45% and 93.38%, respectively, significantly higher than 41.28% and 33.58% of the radiation-alone group, 60.76% and 52.18% of the radiation-gene group, 79.91% and 77.40% of the heating-alone group. It is therefore concluded that this combined application of heating, radiation and gene therapy has a good synergistic and complementary effect and PEI-MZF-NPs can act as a novel non-viral gene vector and magnetic induction medium, which offers a viable approach for the treatment of cancer.

摘要

基于热疗、放疗、基因治疗和化疗综合治疗是癌症治疗的一个有前途的研究领域。本文作者使用聚乙烯亚胺-锰锌铁氧体(PEI-Mn(0.5)Zn(0.5)Fe(2)O(4))纳米粒子(PEI-MZF-NPs)作为基因转染载体,将自行制备的 pEgr1-HSV-TK 转染入 HepG2 细胞,并通过 RT-PCR 检测外源基因 HSV-TK 的表达。结果表明,HSV-TK 成功转染入 HepG2 细胞,HSV-TK 的表达水平稳定。此外,PEI-MZF-NPs 可用作磁热疗的磁性介质,通过磁致加热联合放射-基因治疗治疗肝癌。体外和体内结果均表明,基因、放射和热疗的联合治疗比任何单一治疗都具有更好的治疗效果。联合治疗组的细胞凋亡率和坏死率分别为 51.84%和 15.45%,而放射-基因组分别为 20.55%和 6.80%,放射组分别为 7.49%和 3.62%,热疗组分别为 15.23%和 7.90%,空白对照组分别为 3.52%和 2.16%。联合治疗组的细胞增殖抑制率(88.5%)明显高于放射-基因组(59.5%)、放射组(37.6%)和热疗组(60.6%)。联合治疗组的肿瘤体积和质量抑制率分别为 94.45%和 93.38%,明显高于放射组(41.28%和 33.58%)、放射-基因组(60.76%和 52.18%)和热疗组(79.91%和 77.40%)。因此,本研究认为加热、放疗和基因治疗的联合应用具有良好的协同互补作用,PEI-MZF-NPs 可作为新型非病毒基因载体和磁诱导介质,为癌症的治疗提供了一种可行的方法。

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