基于介孔二氧化硅多功能纳米材料的制备及生物应用

发布时间：2018-05-06 20:52

本文选题：介孔二氧化硅 + 荧光成像　；参考：《东北师范大学》2015年博士论文

【摘要】：纳米科学与技术的快速发展极大地促进了纳米材料在生物与医学领域的广泛应用。特别是近些年来,介孔二氧化硅(m Si O2)纳米材料由于具有可连续调节的介孔孔径、可控的尺寸、稳定的骨架结构、易于修饰的内外表面和良好的生物相容性,并且其丰富的孔道内可贮存各种药物分子,对药物也可起到缓释的作用,在生物医学领域引起了广泛的关注。此外,以m Si O2为主体材料,结合不同功能的客体材料,如金、银纳米粒子、磁性纳米粒子、量子点、荧光分子、靶向生物分子等,在荧光成像、磁共振成像、药物的靶向输送等方面存在良好的发展前景。本论文中合成了基于m Si O2的多功能纳米材料并探讨其在药物运输,可控释放等生物领域中的作用。具体研究内容如下:(1)合成聚乙烯亚胺(PEI)修饰荧光m Si O2包覆Fe3O4蛋黄-蛋壳纳米胶囊与小干扰RNA(si RNA)结合,特定的沉默细胞内基因,同时可以达到荧光示踪,外加磁场诱导si RNA输送。结果显示我们合成的纳米粒子作为si RNA载体能有效的输送si RNA,并释放达到基因沉默的目的。(2)开发一种简单,通用,绿色,温和的方法制备Fe3O4@m Si O2蛋黄-蛋壳纳米胶囊并在其表面覆盖一层聚乙烯亚胺(PEI),水中50°C刻蚀,得到均一的蛋黄-蛋壳纳米胶囊。此方法可拓展合成含有不同蛋黄-m Si O2壳的纳米胶囊。在PEI-Fe3O4@m Si O2蛋黄-蛋壳纳米胶囊表面连接靶向基团并负载抗癌症药物阿霉素(DOX),化学靶向与磁靶向协同作用于肝癌细胞,达到治疗癌症的目的。(3)以聚丙烯酸(PAA)组装在金(Au)纳米粒子的表面得到双面神结构Au-PAA纳米粒子后,选择性在PAA网络结构上水解正硅酸乙酯(TEOS),形成小的Si O2堆积成具有介孔结构的m Si O2纳米簇。通过Au的再生长得到章鱼形Au-PAA/m Si O2双面神纳米粒子。得到纳米材料一面具有PAA的强吸水性和m Si O2多孔性使其具有超高载药量,可在p H改变成酸性时可控释放。同时,由于其在近红外有吸收,也可通过近红外激光照射促进药物分子的扩散,达到双模式药物释放,同时达到光热治疗的目的。最终,检测该纳米材料在体外和体内的化学疗法-光热疗法协同作用杀伤肿瘤效果,达到治疗癌症的目的。(4)改进后的一步法合成m Si O2包覆银(Ag)纳米粒子,并在其表面修饰特定的p H敏感纳米阀。在合成的Ag@m Si O2纳米粒子内负载抗菌药物盐酸莫西沙星(MXF),探讨银纳米粒子与药物分子协同作用于巨噬细胞内的土拉弗朗西斯菌的效果。
[Abstract]:The rapid development of nanoscience and technology has greatly promoted the wide application of nanomaterials in the field of biology and medicine. Especially in recent years, mesoporous silica / m Sio _ 2 nanomaterials are characterized by their continuous adjustable mesoporous pore size, controllable size, stable skeleton structure, easy modification of internal and external surfaces and good biocompatibility. And its abundant pore can store all kinds of drug molecules, and it can also play the role of slow release, which has attracted wide attention in the field of biomedicine. In addition, using m-SiO _ 2 as host material, combining with different functions of guest materials, such as gold, silver nanoparticles, magnetic nanoparticles, quantum dots, fluorescent molecules, targeted biomolecules, etc., in fluorescence imaging, magnetic resonance imaging, etc. There is a good prospect for the targeted delivery of drugs. In this paper, multifunctional nanomaterials based on mSiO _ 2 were synthesized and their roles in drug transport, controlled release and other biological fields were discussed. The specific contents of the study are as follows: (1) Synthesis of polyvinyleneimine (PEI) modification of fluorescent mSiO _ 2 coated with Fe3O4 yolk-eggshell nanocapsule and small interference RNA(si), specific silencing of intracellular genes, and fluorescence tracer. Si RNA transport is induced by external magnetic field. The results show that our synthesized nanoparticles can effectively transport siRNAs as si RNA carriers, and release siRNAs for gene silencing) to develop a simple, universal, green, The Fe3O4@m Sio 2 yolk / eggshell nanocapsule was prepared by mild method and coated with polyethyleneimide (PEI) on its surface. The homogeneous eggyolk eggshell nanocapsule was obtained by 50 掳C etching in water. This method can be used to synthesize nano capsules containing different egg yolk-m Sio 2 shells. On the surface of PEI-Fe3O4@m Sio 2 yolk and eggshell nanocapsule, the target group was connected and the anti-cancer drug adriamycin doxamine was loaded on the surface of the capsule. The chemically targeted and magnetically targeted hepatoma cells were treated synergistically. To achieve the goal of cancer treatment, Au-PAA nanoparticles were assembled on the surface of au) by polyacrylic acid (PAA). The tetraethyl orthosilicate (TEOS) was selectively hydrolyzed on the PAA network to form a small Sio _ 2 stacked into mesoporous mesoporous mSiO _ 2 nanoclusters. The octopus shaped Au-PAA/m Sio 2 nanoparticles were obtained by the regrowth of au. The results show that the nano-materials have the strong water absorption of PAA and the porosity of m-SiO _ 2 on the one hand, which makes the nanocrystalline materials have ultra-high loading amount, and can be released under controlled conditions when pH changes to acid. At the same time, because of its absorption in NIR, it can also promote the diffusion of drug molecules by NIR laser irradiation, and achieve the release of bimodal drugs, as well as the aim of photothermal therapy. Finally, the synergistic effect of chemotherapy-photothermal therapy on tumor in vitro and in vivo was detected, and the modified one-step method was used to synthesize mSiO _ 2 coated silver nanoparticles. And modified on its surface a specific pH sensitive nano valve. The antibacterial drug moxifloxacin hydrochloride (moxifloxacin hydrochloride) was loaded into the synthesized Ag@m Sio 2 nanoparticles to investigate the effect of silver nanoparticles and drug molecules on the interaction of silver nanoparticles with drug molecules in macrophages.
【学位授予单位】：东北师范大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：TB383.1;O613.72

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