论文部分内容阅读
目的:研究新型氨基修饰的磁性介孔二氧化硅纳米颗粒的生物相容性以及跨膜转运能力，并观察该纳米颗粒的体内代谢分布，以此评价该纳米颗粒在基因或药物载体方面的应用前景。方法:制备新型介孔二氧化硅纳米颗粒，以20 nm Fen 3On 4为核心包裹的二氧化硅颗粒，并且进行修饰使之表面氨基化，对此氨基修饰的磁性介孔二氧化硅纳米颗粒细胞毒性研究，携带N-甲基-D-天冬氨酸(NMDA)受体NR2B亚单位基因小干扰RNA(siRNA)质粒细胞转染实验，以及白鼠活体注射靶向模拟实验研究其在体内的生物分布。采用单因素方差分析。n 结果:该新型氨基修饰的磁性介孔二氧化硅纳米颗粒是一种直径在80～100 nm之间，孔径在2～4 nm之间的均一球体型纳米颗粒。在5～125 μg/ml浓度范围内，介孔二氧化硅纳米颗粒的对于细胞活性影响差异无统计学意义(n P>0.05)，始终保持在6%以下。在姜黄素染色的装载有NR2B siRNA质粒的该纳米颗粒转染实验中，可以在荧光显微镜下观察到细胞内的荧光现象。在体外红外测定仪观察红外激发荧光染料标记的纳米颗粒实验中，可见该纳米颗粒在小鼠体内不会有蓄积作用，其最终会通过肾脏随尿液汇聚至膀胱，并最终排出体外。同时在外加磁场的情况下，会有大量荧光颗粒向磁场方向聚集，并且在撤出磁场后不会蓄积，浓度会持续下降。n 结论:氨基化磁性介孔二氧化硅颗粒具有较好的装载能力以及生物安全性，可以携带NR2B基因siRNA质粒通过胞吞作用进入细胞，在外加磁场诱导下可靶向到达病灶区域，为靶向基因治疗奠定基础。“,”Objective:To explore the biocompatibility and transmembrane transport capacity of the new amino-modified magnetic mesoporous silica nanoparticles and observe metabolic profile of the nanoparticles n in vivo, in order to evaluate the possibility of these nanoparticles performing in gene or drug carriers prospect.n Methods:Prepare the new mesoporous silica nanoparticles and packaging with 20nm iron oxide core, then amino-modified. After finishing producing these nanoparticles, we do several examinations about this MSNs, including cytotoxicity, cell plasmid carrying the N-methyl-D-aspartate (NMDA) receptor NR2B subunit gene small interfering RNA (siRNA) transfection experiments, as well as the mesoporous silica nanoparticles in cell culture in order to study their distribution in cells and mice n in vivo. and injection simulation to study the n in vivo biological distribution.n Results:The new magnetic amino-modified mesoporous silica nanoparticles with a diameter between 80-100nm, aperture size 2-4 nm, uni-ball-shape. Exposing in 5 μg/ml-125 μg/ml concentration range, no significant difference in the activity of cells in the mesoporous silica nanoparticles was found. In the flow cytometry analysis, with the increasing concentration, the apoptosis of cells appear slightly increased, but remain below 6% in total. Curcumin staining loaded with the nanoparticle NR2B siRNA plasmid transfection experiments, the phenomenon can be observed intracellular fluorescence under a fluorescence microscope. n In vitro observation of infrared detector infrared excitation fluorescent dye-labeled nanoparticle experiments, showing that the nanoparticles will not accumulate in mice, which will eventually converge with the urine throμgh the kidneys to the bladder, and eventually excreted. While in the case of an applied magnetic field, there will be a large number of fluorescent particles in the magnetic field direction of the gathering, and after the withdrawal of the magnetic field does not accumulate, concentrations continued to decline.n Conclusion:Aminated magnetic mesoporous silica particles, because its excellent loading capacity, better biosecurity and transmembrane transport capacity. Therefore we carry out the biological safety trials of MSN, and lay the foundation for the ultimately efficient, safe mesoporous silica vector used for gene therapy of cancer pain.