用于动脉粥样硬化诊疗的纳米粒子构建

发布时间：2018-02-01 20:53

本文关键词： PAMAM树枝状分子动脉粥样硬化成像动脉粥样硬化治疗光敏感　出处：《吉林大学》2016年博士论文　论文类型：学位论文

【摘要】：近30年来,心脑血管疾病的发病率一直居高不下,严重危害着人类生命健康,而作为诱发心脑血管疾病的重要病理基础——动脉粥样硬化还有很多研究的空间,虽然现在对动脉粥样硬化这种疾病的诊断与治疗手段已经成型,但目前的诊疗手段都存在一定的滞后性,若能在疾病的早期及时发现病患并加以治疗,将会大大的减少该疾病所带来的危害。因此,我们针对这一问题,设计并合成了多种多功能诊疗纳米粒子体系,并对各种体系的合成及性能作测试与表征,具体有如下工作:利用发散法合成了星形PAMAM树枝状分子,之后对合成的树枝状分子进行修饰,得到了不同的PAMAM配体,带有配体的树枝状分子可以和氧化铁纳米粒子或者量子点等发生配体交换反应,在改变其溶解性的同时,还能够保持其原有的光学性质或超顺磁性,且保持较小的粒径,为后续的多功能修饰提供了基础。通过双羧基PEG为桥接,将靶向动脉粥样硬化处MPO的靶分子5-羟色胺(5-HT)链接至G3.0 PAMAM表面,将造影剂Gd通过DTPA的络合作用接入上述分子,再通过配体交换将产物交换到氧化铁纳米粒子表面,从而构成了T1、T2复合靶向性核磁造影诊断体系。针对动脉粥样硬化的病理特点,选用对光敏感的临硝基苄基作为药物释放开关,将治疗动脉粥样硬化药物氟伐他汀通过临硝基苄基连接至G3.0 PAMAM上,在特定波长光照下,统计其药物释放水平,结果证明了该体系作为光敏药物释放体系具有较高的药物释放率。本论文所设计并合成的多功能诊疗体系针对动脉粥样硬化的早期诊断与治疗具有很重要的潜在价值。
[Abstract]:In recent 30 years, the incidence of cardiovascular and cerebrovascular diseases has been high, seriously endangering human life and health. As an important pathological basis to induce cardiovascular and cerebrovascular diseases, there is still a lot of room for research on atherosclerosis, although the diagnosis and treatment of this disease has taken shape. However, the current diagnosis and treatment methods have a certain lag, if the disease can be found in the early and timely treatment, will greatly reduce the harm caused by the disease. Therefore, we aim at this problem. A variety of multifunctional nanoparticle systems for diagnosis and treatment were designed and synthesized, and the synthesis and properties of these systems were tested and characterized. The main work is as follows: star PAMAM dendrimer was synthesized by divergence method. The dendritic molecules were modified to obtain different PAMAM ligands. The dendrimers with ligand could exchange ligand with iron oxide nanoparticles or quantum dots. While changing its solubility, it can also maintain its original optical properties or superparamagnetism, and maintain a smaller particle size, which provides the basis for the subsequent multifunctional modification, which is bridged by dicarboxylic PEG. The target molecule of MPO targeted at atherosclerosis, 5-HT), was linked to the surface of G3.0 PAMAM, and the contrast agent Gd was connected to the molecule by the complexation of DTPA. Then the product was exchanged to the surface of iron oxide nanoparticles by ligand exchange, which formed the diagnostic system of T1T2-targeted nuclear magnetic resonance imaging, aiming at the pathological characteristics of atherosclerosis. The photo-sensitive p-nitrobenzyl group was selected as the drug release switch, and fluvastatin was connected to G 3.0 PAMAM through the p-nitrobenzyl group for the treatment of atherosclerosis under specific wavelength illumination. Count the drug release level. The results show that this system has high drug release rate as a drug release system of Guang Min. The multifunctional diagnosis and treatment system designed and synthesized in this paper has important potential for early diagnosis and treatment of atherosclerosis. Value.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R543.5;TB383.1

【参考文献】