水溶液中碳纳米管的物理化学表征及其血液相容性研究
本文选题:碳纳米管 + 理化表征 ; 参考:《北京协和医学院》2012年硕士论文
【摘要】:碳纳米管的独特理化性质使其在生物医学领域有着广阔的应用前景。迄今为止,已有大量的研究报道碳纳米管可能在药物、基因或蛋白的载体和分子成像的造影剂方面有诱人的应用价值。碳纳米管在生物医学领域的应用的前提之一是在水溶液中均匀、稳定分散。但是分散在水溶液中的碳纳米管很难用传统的分析技术来进行理化性质表征。此外,碳纳米管作为生物医药载体应用时,不可避免进入循环血液,了解并对其血液相容性进行评价对于碳纳米管的安全应用具有重要意义。虽然已有诸多文献报道碳纳米管会引起血小板的活化和聚集,促进内源性凝血,降低血管内皮细胞的活性等,但是关于碳纳米管对红细胞的作用以及对凝血过程的影响和血栓力学性质的报道十分有限。 本论文的研究工作主要包括以下三个方面: (1)建立碳纳米管羧基化和氨基化的表面处理方法和制备稳定的碳纳米管水分散液。 (2)对碳纳米管进行物理化学表征,建立针对分散在水溶液中的碳纳米管的物理化学表征体系。 (3)研究碳纳米管对血液中各成分的作用,特别是对红细胞的作用和对血栓形成过程的影响。 取得的主要研究结果为: (1)通过浓酸超声氧化法制备表面含有羧基等含氧基团的碳纳米管,通过控制超声时间制备得到氧化程度不同的碳纳米管。在羧基化碳纳米管的基础上,通过缩合反应使碳纳米管表面氨基化。将修饰后的碳纳米管通过超声辅助方法制得稳定的碳纳米管水分散液。 (2)以紫外-可见-近红外吸收光谱(UV-vis-NIR)为主,结合扫描电镜(SEM)、动态光散射仪(DLS)、热重法(TGA)、X-射线光电子谱仪(XPS)和傅里叶红外光谱仪(FTIR)对水溶液中的碳纳米管进行表征。将特征吸收光谱进行分峰拟合处理,建立了主峰峰位和强度与碳纳米管尺寸以及表面含氧量的关系。并采用吸收光谱方法对表征了碳纳米管在水中分散稳定性的规律。 (3)碳纳米管与血液共孵育后对血液系统中各成分均造成不同程度的损伤,引起红细胞形态皱缩甚至细胞膜破裂。当碳纳米管具有相同尺寸时,氨基化的MWCNTs对红细胞的破坏作用要强于羧基化的碳纳米管;当碳纳米管具有相同的表面化学组成时,短碳纳米管对红细胞的破坏作用要大于长碳纳米管。四种碳纳米管均引起了血小板中等强度的活化(10%-25%),长碳纳米管激活血小板的水平要强于短碳纳米管。同时长氨基化碳纳米管引起红细胞和血小板数量减少。四种碳纳米管均能使初凝时间提前,凝血时间改变和影响血凝块的力学性质。在相同的凝血时间内,氨基化碳纳米管使血凝块硬度升高,而羧基化碳纳米管使血凝块硬度降低。四种碳纳米管对血管内皮细胞均造成中等程度的损伤。
[Abstract]:The unique physicochemical properties of carbon nanotubes (CNTs) make them promising in biomedical applications. Up to now, many studies have reported that carbon nanotubes may have attractive application value in drug, gene or protein carrier and molecular imaging contrast agent. One of the prerequisites for the application of carbon nanotubes in biomedical applications is the uniform and stable dispersion of carbon nanotubes in aqueous solutions. However, it is difficult to characterize the physicochemical properties of carbon nanotubes dispersed in aqueous solution by traditional analytical techniques. In addition, when carbon nanotubes are used as biomedical carriers, they inevitably enter the circulation of blood. It is of great significance to understand and evaluate their blood compatibility for the safe application of carbon nanotubes. Although there have been many reports that carbon nanotubes can cause platelet activation and aggregation, promote endogenous coagulation, reduce the activity of vascular endothelial cells, and so on. However, the effects of carbon nanotubes on red blood cells, coagulation process and the mechanical properties of thrombus are very limited. The research work of this thesis mainly includes the following three aspects: A surface treatment method for carboxylation and aminolysis of carbon nanotubes (CNTs) and the preparation of stable water dispersions of CNTs were established. 2) the physicochemical characterization of carbon nanotubes was carried out, and the physicochemical characterization system of carbon nanotubes dispersed in aqueous solution was established. (3) to study the effects of carbon nanotubes (CNTs) on blood components, especially on red blood cells (RBC) and thrombosis process. The main findings obtained are: 1) carbon nanotubes with carboxyl and other oxygen groups on the surface were prepared by concentrated acid ultrasonic oxidation, and carbon nanotubes with different degree of oxidation were prepared by controlling ultrasonic time. On the basis of carboxyl carbon nanotubes, the surface of carbon nanotubes was aminated by condensation reaction. Stable water dispersions of carbon nanotubes were prepared by ultrasonic assisted method. The carbon nanotubes in aqueous solution were characterized by UV-vis-NIR (UV-vis-NIR), scanning electron microscopy (SEM), dynamic light scattering (DLSX), thermogravimetric TGAGA-X- ray photoelectron spectrometer (TGA) and Fourier transform infrared spectroscopy (FTIR). The relationship between the position and intensity of the main peak and the size of carbon nanotubes and the oxygen content on the surface was established by fitting the characteristic absorption spectra. The dispersion stability of carbon nanotubes in water was characterized by absorption spectra. (3) carbon nanotubes (CNTs) co-incubated with blood caused various components of the blood system to different degrees of damage, resulting in erythrocyte morphological shrinkage and even cell membrane rupture. When the carbon nanotubes have the same size, the amino MWCNTs is more destructive to the red blood cells than the carboxylated carbon nanotubes, and when the carbon nanotubes have the same surface chemical composition, Short carbon nanotubes are more destructive to red blood cells than long carbon nanotubes. All four carbon nanotubes cause moderate activation of platelets. Long carbon nanotubes activate platelets more than short carbon nanotubes. At the same time, long carbon nanotubes (CNTs) cause a decrease in the number of red blood cells and platelets. Four kinds of carbon nanotubes can advance the initial coagulation time, change the coagulation time and affect the mechanical properties of blood clots. At the same coagulation time, the hardness of hemagglutination was increased by amino carbon nanotubes, while the hardness of blood clots was decreased by carboxylated carbon nanotubes. All four carbon nanotubes caused moderate damage to vascular endothelial cells.
【学位授予单位】:北京协和医学院
【学位级别】:硕士
【学位授予年份】:2012
【分类号】:R318.08
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