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磁性纳米颗粒作为基因传递载体:在振荡磁体阵列存在下增强转染

Magnetic nanoparticles as gene delivery agents: enhanced transfection in the presence of oscillating magnet arrays.

作者信息

McBain S C, Griesenbach U, Xenariou S, Keramane A, Batich C D, Alton E W F W, Dobson J

机构信息

Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent ST4 7QB, UK.

出版信息

Nanotechnology. 2008 Oct 8;19(40):405102. doi: 10.1088/0957-4484/19/40/405102. Epub 2008 Aug 20.

Abstract

Magnetic nanoparticle-based gene transfection has been shown to be effective in combination with both viral vectors and with non-viral agents. In these systems, therapeutic or reporter genes are attached to magnetic nanoparticles which are then focused to the target site/cells via high-field/high-gradient magnets. The technique has been shown to be efficient and rapid for in vitro transfection and compares well with cationic lipid-based reagents, producing good overall transfection levels with lower doses and shorter transfection times. In spite of its potential advantages (particularly for in vivo targeting), the overall transfection levels do not generally exceed those of other non-viral agents. In order to improve the overall transfection levels while maintaining the advantages inherent in this technique, we have developed a novel, oscillating magnet array system which adds lateral motion to the particle/gene complex in order to promote transfection. Experimental results indicate that the system significantly enhances overall in vitro transfection levels in human airway epithelial cells compared to both static field techniques (p<0.005) and the cationic lipids (p<0.001) tested. In addition, it has the previously demonstrated advantages of magnetofection-rapid transfection times and requiring lower levels of DNA than cationic lipid-based transfection agents. This method shows potential for non-viral gene delivery both in vitro and in vivo.

摘要

基于磁性纳米颗粒的基因转染已被证明与病毒载体和非病毒载体联合使用时均有效。在这些系统中,治疗性基因或报告基因附着于磁性纳米颗粒上,然后通过高场/高梯度磁体将其聚焦至靶位点/细胞。该技术已被证明在体外转染中高效且快速,与基于阳离子脂质的试剂相比效果良好,能以更低剂量和更短转染时间产生良好的总体转染水平。尽管其具有潜在优势(特别是在体内靶向方面),但总体转染水平一般不超过其他非病毒载体。为了在保持该技术固有优势的同时提高总体转染水平,我们开发了一种新型的振荡磁体阵列系统,该系统为颗粒/基因复合物增加横向运动以促进转染。实验结果表明,与静态场技术(p<0.005)和所测试的阳离子脂质(p<0.001)相比,该系统显著提高了人呼吸道上皮细胞的总体体外转染水平。此外,它具有磁转染先前已证明的优势——转染时间短,且与基于阳离子脂质的转染试剂相比所需的DNA水平更低。该方法在体外和体内的非病毒基因递送方面均显示出潜力。

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