Using thermal energy produced by irradiation of Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) for heat-inducible gene expression.
Using thermal energy produced by irradiation of Mn-Zn ferrite magnetic nanoparticles (MZF-NPs) for heat-inducible gene expression.
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DOI：
10.1016/j.biomaterials.2008.01.038
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发表时间：
2008-06
期刊：
影响因子：
14
通讯作者：
Q. Tang;Dong‐sheng Zhang;Xiao-ming Cong;Mei-ling Wan;Li-qiang Jin
中科院分区：
文献类型：
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作者：
Q. Tang;Dong‐sheng Zhang;Xiao-ming Cong;Mei-ling Wan;Li-qiang Jin
基因治疗相对于传统治疗的主要优势之一是靶向治疗基因在所需细胞或组织中的表达的潜力。为了实现靶向基因表达，我们开发了一种新的热诱导基因表达系统，在该系统中，由锰锌铁氧体磁性纳米颗粒（MZF-NPs）在交变磁场（AMF）下产生的热能被用于激活基因表达。采用共沉淀法制备了MZF纳米粒子，并对其进行了阳离子聚乙烯亚胺（PEI）表面改性。然后对不同剂量的MZF-NPs进行体内和体外热力学测试。PEI-MZF-NPs具有良好的DNA结合能力和高转染效率。在AMF中，它们可以上升到稳定的温度。为了分析AMF下热诱导的基因表达，我们将P1730 OR载体转染与MZF-NPs照射产生的热疗相结合。通过使用LacZ基因作为报告基因和Hsp 70作为启动子，证明了在组织培养细胞中，通过中度高温（在生长培养基中添加12.24或25.81mg MZF-NPs），异源基因的表达可以提高到背景的10至500倍。注射2.6或4.6mg MZF-NPs后，荷瘤裸鼠体温分别升高至39.5或42.8°C，β-gal浓度分别升高至3.8或8.1mU/mg蛋白。因此，我们的研究结果支持高温下的AMF作为一种可行的方法，有针对性的热诱导的基因表达的照射MZF纳米粒子。该系统利用MZF-NPs相对较低的居里点来控制体内热疗温度，从而获得安全有效的热诱导转基因表达。
One of the main advantages of gene therapy over traditional therapy is the potential to target the expression of therapeutic genes in desired cells or tissues. To achieve targeted gene expression, we developed a novel heat-inducible gene expression system in which thermal energy generated by Mn–Zn ferrite magnetic nanoparticles (MZF-NPs) under an alternating magnetic field (AMF) was used to activate gene expression. MZF-NPs, obtained by co-precipitation method, were firstly surface modified with cation poly(ethylenimine) (PEI). Then thermodynamic test of various doses of MZF-NPs was preformed in vivo and in vitro. PEI–MZF-NPs showed good DNA binding ability and high transfection efficiency. In AMF, they could rise to a steady temperature. To analyze the heat-induced gene expression under an AMF, we combined P1730OR vector transfection with hyperthermia produced by irradiation of MZF-NPs. By using LacZ gene as a reporter gene and Hsp70 as a promoter, it was demonstrated that expression of a heterogonous gene could be elevated to 10 to 500-fold over background by moderate hyperthermia (added 12.24 or 25.81mg MZF-NPs to growth medium) in tissue cultured cells. When injected with 2.6 or 4.6mg MZF-NPs, the temperature of tumor-bearing nude mice could rise to 39.5 or 42.8°C, respectively, and the β-gal concentration could increase up to 3.8 or 8.1mU/mg proteins accordingly 1 day after hyperthermia treatment. Our results therefore supported hyperthermia produced by irradiation of MZF-NPs under an AMF as a feasible approach for targeted heat-induced gene expression. This novel system made use of the relative low Curie point of MZF-NPs to control the in vivo hyperthermia temperature and therefore acquired safe and effective heat-inducible transgene expression.