磁性空心介孔氧化硅标记血小板对颈动脉血栓的核磁成像研究

发布时间：2018-03-14 02:36

本文选题：空心介孔无机硅纳米囊　切入点：血小板　出处：《西南科技大学》2017年硕士论文　论文类型：学位论文

【摘要】：全球范围内,心血管疾病的致死率已经超过肿瘤,成为最主要的致死原因,而血栓形成是脑卒中、冠心病等心脑血管疾病的主要病例基础,但是血栓的早期诊断仍然是临床上的一大挑战。因此对符合临床症状动物模型的成像研究是至关重要的。本工作以血栓精准分子影像的需求为背景,以空心介孔氧化硅为磁性氧化铁的载体,围绕空心介孔氧化硅的生物相容性、血小板靶向血栓的归巢本能,主要开展了以下几个方面的研究:(1)载四氧化三铁空心介孔氧化硅囊(OSNCs)的合成介孔氧化硅具有独特的中空结构、巨大的孔结构和高比表面积,以及良好的生物相容性,是一种可以用来载药,并最具临床价值的纳米材料。本课题首先合成了四氧化三铁纳米颗粒(Fe3O4),采用一步乳化的作用,合成了载Fe3O4空心介孔氧化硅纳米囊(OSNCs)。结果表明该纳米囊的的直径为82nm左右,其表面壳层能成功负载Fe3O4并具有优异的磁学性能,MRIT2弛豫率为303.5mM·s~(-1)。(2)OSNCs对血小板的标记(OSNCs-PLT)考虑到OSNCs的生物相容性及靶向功能的局限性,因此本课题以血小板作为OSNCs靶向血栓的引导物。因为血小板具有识别血管受伤和靶向血栓的能力,因此血小板可以带着OSNCs靶向到血栓部位。TEM及普鲁士蓝染色结果都表明,血小板能成功被标记(标记后血小板记为OSNCs@PLT),当OSNCs贴浓度增加到100μg·mL~(-1)时,血小板的标记率达到12fg·Platelet~(-1)。根据bEnd.3细胞毒性测试,发现血小板会明显降低OSNCs对细胞的毒害作用,细胞活性也从OSNCs的86%提高到了99%左右。同时,OSNCs@PLT的弛豫率为337.4mM·s~(-1),这说明血小板的吞噬,并不会降低OSNCs的弛豫率,同时也说明OSNCs@PLT具有优秀的核磁成像能力。根据血小板聚集实验,可以看到OSNCs@PLT的聚集能力与纯血小板并没有太大的差异,说明血小板的活性并不会因OSNCs的存在而发生改变。(3)OSNCs-PLT对血栓的核磁成像研究FeCl_3建立的血栓模型结构类似于人类临床自发性血栓,改变其时间及浓度,可以形成非闭塞性血栓,该模型有利于造影剂在血液中的循环和造影。根据超声成像及冰冻切片分析,可知道10%FeCl_3作用动脉5min后形成的血栓为非闭塞的混合型血栓。核磁共振成像(MRI)因为空间分辨率高,且具有无创精确诊断能力而被广泛运用于各类疾病的成像研究中。当血栓模型建立后,将大鼠移入到核磁成像仪中进行成像,结果表明,与OSNCs组和Platelets组(PLT)相比,OSNCs@PLT组具有明显的靶向作用和核磁成像效果。
[Abstract]:Globally, the fatality rate of cardiovascular disease has surpassed that of tumor and become the leading cause of death. Thrombosis is the main case base of cardiovascular and cerebrovascular diseases such as stroke, coronary heart disease and so on. But the early diagnosis of thrombus remains a major clinical challenge. Therefore, imaging studies that fit the animal model of clinical symptoms are essential. This work is based on the need for accurate molecular imaging of thrombus. With hollow mesoporous silica as the carrier of magnetic iron oxide, the biocompatibility of hollow mesoporous silica and homing instinct of platelet-targeted thrombus were studied. The synthesis of mesoporous silicon oxide containing iron trioxide hollow mesoporous silicon oxide (OSNCs) has unique hollow structure, large pore structure, high specific surface area, and good biocompatibility. It is a kind of nanomaterials which can be used to carry drugs and has the most clinical value. In this paper, the Fe _ 3O _ 4O _ 4O _ 4O _ 4O _ 4O _ 4 nanoparticles were synthesized and emulsified by one-step emulsification. The hollow mesoporous silica nanocysts OSNCsN supported on Fe3O4 have been synthesized. The results show that the diameter of the nanocysts is about 82 nm. The surface shell layer can successfully load Fe3O4 and has excellent magnetic properties. The relaxation rate of MRIT2 is 303.5 mm 路squi-1n. OSNCs-PLT takes into account the limitations of the biocompatibility and targeting function of OSNCs. Therefore, platelets were used as a guide for OSNCs to target thrombus. Because platelets have the ability to recognize vascular injury and target thrombus, platelets can be targeted to thrombus site with OSNCs and Prussian blue staining. Platelets can be labeled successfully (labeled platelets are called OSNCsprotein PLTT, when the concentration of OSNCs paste increases to 100 渭 g 路mL ~ (-1)), the labeling rate of platelets reaches 12fg 路Plateleteletelet-1a. According to the cytotoxicity test of bEnd.3, it is found that platelets can significantly reduce the toxic effect of OSNCs on cells. The cell activity also increased from 86% of OSNCs to about 99%. The relaxation rate of OSNCsPLT was 337.4 mm 路sb-1, which indicated that the phagocytosis of platelets did not decrease the relaxation rate of OSNCs, but also showed that OSNCs@PLT had excellent nuclear magnetic imaging ability. We can see that the aggregation ability of OSNCs@PLT is not very different from that of pure platelets. The results show that the activity of platelet does not change with the presence of OSNCs. Nuclear magnetic resonance imaging of thrombus. The thrombus model established by FeCl_3 is similar to that of human clinical spontaneous thrombus. By changing its time and concentration, a non-occlusive thrombus can be formed. The model facilitates circulation and angiography of contrast agents in the blood. Based on ultrasound imaging and frozen section analysis, It can be seen that the thrombus formed 5 minutes after 10Cl3 acts on the artery is a non-occlusive mixed thrombus. Magnetic Resonance Imaging (MRI) because of its high spatial resolution, When the thrombus model was established, the rats were transferred to the nuclear magnetic imager for imaging. Compared with OSNCs group and Platelets group, OSNCsPLT group has obvious targeting effect and nuclear magnetic imaging effect.
【学位授予单位】：西南科技大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R54;R445.2

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