物理化学学报 >> 2007, Vol. 23 >> Issue (12): 1857-1863.doi: 10.1016/S1872-1508(07)60090-4

研究论文 上一篇    下一篇

一种新型磁性纳米基因载体的制备与表征

郝丽娟; 李双艳; 韩磊; 黄杰; 常津   

  1. 天津大学材料科学与工作学院纳米生物技术研究所, 天津 300072
  • 收稿日期:2007-07-30 修回日期:2007-09-03 发布日期:2007-11-30
  • 通讯作者: 常津 E-mail:jinchang@tju.edu.cn

Preparation and Characterization of a Novel Magnetic Nano-Gene Vector

HAO Li-Juan; LI Shuang-Yan; HAN Lei; HUANG Jie; CHANG Jin   

  1. Institute of Nanobiotechnology, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, P. R. China
  • Received:2007-07-30 Revised:2007-09-03 Published:2007-11-30
  • Contact: CHANG Jin E-mail:jinchang@tju.edu.cn

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摘要： 制备了一种新的基因载体材料———赖氨酸修饰的壳聚糖(CTS-lys)包裹的磁性纳米颗粒. 优化制备了CTS-lys原料, 红外(IR)和核磁(1H-NMR)检测结果表明壳聚糖的大量氨基被赖氨酸修饰. 通过共沉淀方法, 制备了赖氨酸修饰的壳聚糖磁性纳米颗粒(CTS-lys-MNPs). 利用透射电镜(TEM)、激光粒度分析仪、磁力计(VSM)和X射线衍射(XRD)对CTS-lys-MNPs进行了表征, 并通过U293细胞, 研究了CTS-lys-MNPs的细胞毒性. 结果表明, CTS-lys-MNPs的平均粒径为100 nm, 具有较好的超顺磁性和较低的细胞毒性; 在此基础上, 通过凝胶电泳实验观察了CTS-lys-MNPs和DNA的结合情况, 并通过单光子发射型计算机断层显像仪(SPECT) 研究了CTS-lys-MNPs和DNA的复合物在动物体内跨越血脑屏障的能力. 结果表明, CTS-lys-MNPs 是一种较好的磁靶向基因载体并能成功地跨越血脑屏障.

关键词: 壳聚糖, 赖氨酸, 磁性纳米颗粒, 靶向, 基因载体, 血脑屏障

Abstract: In recent times, as nonviral gene vectors, chitosan and its derivations have attracted many researchers’ attentions. The preparation of a novel gene vector-magnetic nanoparticle coated with a novel polymer-lysine modified chitosan (CTS-lys) is described in this article. Initially, the correlation conditions of preparing CTS-lys were optimized, and it was demonstrated that lots of amines of chitosan were modified by lysine, which was indicated by infrared spectroscopy (IR) and proton nuclear magnetic resonance (1H-NMR). Subsequently, through the coprecipitation method, the lysine modified chitosan magnetic nanospheres (CTS-lys-MNPs) were attained. The characterizations of nanospheres were measured by transmission electron microscopy (TEM), dynamic laser light scattering, vibrating samples magnetometer (VSM), and X-ray diffraction (XRD). The cytotoxicity of CTS-lys-MNPs was also investigated with U293 cells. The results indicated that the average size of nanospheres was about 100 nm, and they had narrower size distribution, good superparamagnetic property, and perfect crystallinity, and they also retained low toxicity. Additionally, the combination of DNA and CTS-lys-MNPs was observed via agarose gel electrophoresis, and the ability of complexes ofCTS-lys-MNPs andDNAcrossingblood-brain barrier (BBB) in ratswas studied by single photon emission computed tomography (SPECT). The results showed that the gene vector was a superior material, which had the ability of targeting and avoiding the caption of BBB.

Key words: Chitosan, Lysine, Magnetic nanospheres, Target, Gene vector, Blood-brain barrier