基于氧化锌、四氧化三铁以及金纳米颗粒的多功能诊疗体系的研究

发布时间：2018-04-15 21:45

本文选题：氧化锌 + 壳聚糖　；参考：《南京大学》2015年硕士论文

【摘要】：随着纳米技术的飞速发展,传统的单一功能载体在很多情况下已经无法满足临床的需求。多功能纳米药物的诞生,很好地解决了这一问题。通过将多种模式的治疗或者诊断功能融合在单一体系当中,可以实现多模态的优势互补。基于此,近年来一系列多功能纳米药物的产生,从多个方面推进了临床研究。本论文中,针对体外量子点研究和体内肝区病变检测问题,我们设计了两种类型不同的多功能纳米载体,并对其治疗或诊断,检测效果加以验证分析,其过程如下：首先,针对了传统荧光标记量子点毒性大的问题。我们选取了一种安全无毒的ZnO量子点。通过溶胶凝胶法合成单一均匀分散的ZnO量子点,并通过一种非溶剂辅助的反离子络合法将ZnO量子点包裹到壳聚糖纳米微球中。由于壳聚糖外层的保护作用,所得的壳聚糖-氧化锌复合纳米微球具有无毒性。包裹在壳聚糖纳米微球中的ZnO量子点与纯ZnO量子点相比其荧光稳定性更好,在细胞中滞留的时间更长。这些壳聚糖-氧化锌复合纳米微球能够发出强的蓝光从而可以用作细胞标记物。阳性的壳聚糖表面及其表面上的亲水性分子为负载抗肿瘤药物如阿霉素等提供了许多结合位点。总的来说所得的壳聚糖-氧化锌复合纳米微球可以用于标记细胞、显示纳米球在细胞中的分布情况从而可以监测负载药物在体内的运输情况,这些特征使得壳聚糖-氧化锌复合纳米微球在细胞荧光标记和肿瘤治疗方面有着良好的发展前景。目前临床缺乏行之有效的准确无创手段对脂肪肝到肝细胞癌病变进行检测。针对这一问题,我们设计合成了一种三模式的纳米草莓型结构Fe3O4-Au纳米粒子。体外荧光分析结果证实复合粒子可以从溶酶体当中逃逸,并保持较高的光稳定性。体内实验结果证实注射Fe3O4-Au纳米粒子后,健康大鼠的肝脏在CT和MR下的对比度均显著增强。进一步地,我们采用疾病模型大鼠来分析增强效果。在脂肪肝大鼠模型中,可以清楚发现肝脏增强造影后对比度均匀升高。而对于脂肪肝和肝细胞癌而言,注射后仅可见肝脏正常实质吞噬纳米粒子信号增强,病变组织与周围对比度极高。病理学和血液学分析证实Fe3O4-Au纳米粒子注射不会引起急性或者慢性的炎症反应,适宜用作体内应用。
[Abstract]:With the rapid development of nanotechnology, the traditional single functional carriers can not meet the clinical needs in many cases.The birth of multi-functional nanopharmaceuticals solves this problem well.Multiple modes of treatment or diagnosis can be integrated into a single system to achieve multi-modal complementary advantages.Based on this, a series of multifunctional nanopharmaceuticals have been produced in recent years, which has promoted clinical research in many aspects.In this thesis, we designed two different types of multifunctional nano-carriers to study in vitro quantum dots and detect liver lesions in vivo. The results of treatment, diagnosis and detection were verified and analyzed. The process is as follows: first,In order to solve the problem of high toxicity of traditional fluorescent labeled QDs.We selected a safe and nontoxic ZnO quantum dot.A single uniformly dispersed ZnO quantum dot was synthesized by sol-gel method, and ZnO quantum dots were encapsulated into chitosan nanospheres by a non-solvent assisted counterion complexation method.Because of the protective effect of chitosan, the chitosan-zinc oxide composite nanospheres are non-toxic.Compared with pure ZnO quantum dots, ZnO quantum dots encapsulated in chitosan nanoparticles have better fluorescence stability and longer retention time in cells.These chitosan-zinc oxide composite nanospheres emit strong blue light and can be used as cell markers.The positive chitosan surface and its surface hydrophilic molecules provide many binding sites for loaded antitumor drugs such as adriamycin.In general, the resulting chitosan / zinc oxide composite nanospheres can be used to label cells and show the distribution of the nanospheres in the cells, thus monitoring the transport of the loaded drugs in the body.These characteristics make chitosan-zinc oxide composite nanospheres have a good prospect in cell fluorescence labeling and tumor therapy.At present, there is a lack of effective and accurate noninvasive method to detect fatty liver to hepatocellular carcinoma.To solve this problem, we designed and synthesized a three-mode Fe3O4-Au nanoparticles with strawberry structure.Fluorescence analysis in vitro confirmed that the composite particles could escape from lysosomes and maintain high photostability.The results of in vivo experiments confirmed that the contrast of liver of healthy rats was significantly enhanced under CT and Mr after injection of Fe3O4-Au nanoparticles.Further, we used the disease model rats to analyze the enhancement effect.In the rat model of fatty liver, it can be clearly found that the contrast of liver is increased homogeneously after contrast enhancement.However, for fatty liver and hepatocellular carcinoma, only normal liver parenchyma phagocytosis signal was enhanced after injection, and the contrast between pathological tissue and surrounding tissue was very high.Pathological and hematological analysis confirmed that Fe3O4-Au nanoparticles injection does not cause acute or chronic inflammatory response and is suitable for use in vivo.
【学位授予单位】：南京大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TB383.1

【共引文献】