【作者】 刘芳；

【导师】 王柯敏； 何晓晓；

【作者基本信息】 湖南大学 ， 分析化学， 2006， 硕士

【摘要】 纳米技术的快速发展为纳米材料在生物医学领域的应用开辟了一个崭新的局面，在研究与开发纳米材料的同时，纳米材料的生物效应即生物安全性问题也逐渐成为科研工作者研究的新焦点。作为众多纳米材料重要成员之一的硅壳纳米颗粒，由于制备简单、易于生物修饰等优点在生物医学领域得到了广泛应用，但是有关硅壳纳米颗粒的生物效应研究还缺乏深入系统的研究。本论文瞄准硅壳纳米颗粒的细胞生物效应，开展了一系列的研究，并在此基础上发展了一种稳定性好，又易于生物修饰的多基团修饰的硅壳纳米颗粒。本论文的主要内容包括以下三个方面： 1、以多种评价方法对包裹RuBpy染料的硅壳纳米颗粒对美洲绿猴肾细胞（COS-7）、人脐静脉上皮细胞（EVC304）和正常肝细胞（L02细胞）的生物效应进行了系统地考察。结果表明，一定浓度范围内硅壳纳米颗粒对三种细胞系的生长、繁殖均未产生明显的毒副作用；纳米颗粒进入细胞内后，细胞依然保持良好的形态和生长状况。 2、从硅壳纳米颗粒对人以及周围环境的影响角度出发，探讨纯硅壳纳米颗粒（SiNP）、磷酸化硅壳纳米颗粒（PO₄NP）和氨基化硅壳纳米颗粒（NH₂NP）与人皮肤角质形成细胞系（HaCaT）的生物效应。结果发现，SiNP、PO₄NP以及NH₂NP三种颗粒对HaCaT细胞的影响均存在浓度依赖关系，且毒性大小顺序为：NH₂NP＞SiNP＞PO₄NP；同时，HaCaT细胞对纳米颗粒的吞噬量和吞噬速度也因其表面修饰的不同而存在差异，在同样的作用浓度和作用时间下，NH₂NP进入到细胞的量最多、速度最快，SiNP次之，PO₄NP则最少、最慢。 3、在上述工作的基础上，通过对硅壳纳米颗粒表面基团活化和稳定性研究，比较得出一种简单的在纳米颗粒表面引入不同功能化基团的方法：并通过在颗粒表面引入适量比例的磷酸基团和氨基，制备出一种稳定性好，易于实现生物功能化的多基团修饰的硅壳纳米颗粒，为硅颗粒在生物医学领域的应用提供新的契机。更多还原

【Abstract】 With the fast development of nanotechnology, the application of nanomaterials in biomedicine has been to a new phase. So the bioeffects of the nanomaterials have gradually become a new focus in the research fields flowing the research and exploitation of nanomaterials. Recently, silica nanoparticles as one of the important nanomaterials display several features of straightforward synthesis and easily modification, which make them be widely applied in biomedicine. However, the bioeffects of silica shell nanoparticles have not been systemicly studied. This thesis is aimed at the cell bioeffects of silica shell nanoparticles. A series of studies on cell bioeffects of silica nanoparticles have been operated. And a kind of muli-groups modified silica nanoparticles with good stability and also easy modification has been developed. This thesis is composed of the following three parts:1. The bioeffects of RuBpy silica nanoparticles on COS-7、EVC304 and L02 cells have been studied by use of different evaluation methods. The results indicated that no measurable cytotoxic effects of nanoparticles being observed on the growth and proliferation of the three kinds of cell lines at a certain range of nanoparticles concentration. Moreover, cells still remained good shape and growth state after the uptake of nanoparticels.2. In order to probe the effect of silica nanoparticles on environment or human, the bioeffects of silica nanoparticles （SiNP）, phosphorylate-terminated nanoparticles （PO₄NP） and amino-terminated nanoparticles （NH₂NP） on HaCat cell line has been investigated. Results indicated that the bioeffects of the three kinds of nanoparticles on HaCaT cells were concentration-dependent, and the following order was observed: NH₂NP> SiNP> PO₄NP. In addition, the quantity and rapidity of cellular uptake of nanoparticles by HaCaT cells were diverse due to the different functional groups. Under the same conditions, NH₂NP was most and fast internalized by HaCaT cells, followed by SiNP, and PO₄NP was the least and slowest.3. We studied the surface modification and stability of silica nanoparticles based on the two front parts of work. A simple method that can be more readily conjugate different function groups to the nanoparticles surface was obtained. And a kind of muli-groups modified silica nanoparticles with maximal stability and easy modification by conjugated an optimum proportional phosphate groups and amino groups has been developed, which provided a new chance for the application of silica更多还原