生物可降解的焦糖化碳球负载锰在核磁成像和光热治疗中的应用

发布时间：2018-04-24 23:10

本文选题：焦糖化碳纳米颗粒 + 光热治疗　；参考：《山东大学》2017年硕士论文

【摘要】：癌症是威胁人类健康的一种恶性疾病,实现癌症的精确诊断和治疗对于提高癌症的治愈率是非常重要的。核磁共振成像具有无辐射、高的分辨率、高准确度、多参数成像的优点,是一种常用的诊断技术。在核磁成像过程中,为了提高对比度,需要用到磁共振成像对比剂。光热治疗是一种治疗癌症的新方法,具有精确度高和损伤小的优点,在光热治疗中具有高光热转化效率的光热治疗剂是非常重要的。随着纳米材料的发展,由于纳米材料独特的光学、磁学和电学性质,使得纳米材料在生物医学上的应用得到广泛研究。磁共振成像对比剂分为T1和T2两种,锰的纳米材料作为磁共振成像的对比剂,可以有效的提高T1成像效果。光热治疗剂一般包括机染料物质、贵金属材料、碳类材料和半导体材料。集诊断和治疗于一体的多功能的纳米材料被广泛研究,但是纳米材料在生物体内的毒性和代谢问题,是阻碍纳米材料在临床上使用的重大障碍,也是人们一直关注的问题。在本文中,我们从食品科学的角度出发,以食品焦糖化反应为合成方法,用葡萄糖合成生物相容性好的和可生物降解的焦糖化碳纳米材料,焦糖化碳纳米颗粒表面含有大量的官能团可以形成锰碳纳米材料,用于癌症的核磁成像和光热治疗研究。具体内容归纳如下:1.我们通过自牺牲氧化还原的方法合成了生物相容性的焦糖化碳纳米颗粒负载顺磁性超薄四氧化三锰纳米片的复合材料,用于肝核磁成像的T1对比剂和T1加权成像研究,这种纳米材料能够被枯否氏细胞吞噬而且有很高的弛豫率。我们研究了 Mn304-CNPs的合成以及作为磁共振成像的特征。Mn3O4-CNPs的弛豫率(r1)达到11.6mM-1s-1是临床上使用的钆的螯合物的弛豫率的近3倍。在注射纳米材料4h后,小鼠的肝脏信号增强50.1%。锰在小鼠内的含量在注射纳米材料48h后与注射前相等。因此,Mn3O4-CNPs能用于肝核磁成像的对比剂。2.我们通过离子吸附和配位作用合成了可生物降解的、具有pH响应的碳纳米颗粒负载Mn~(2+)(Mn~(2+)-CNPs)用于肿瘤的核磁成像和光热治疗。Mn~(2+)-CNPs纳米材料经过激光照射后,有很好的光热效果。在pH是5的条件下,锰离子的释放率达到45%,说明有pH响应效果。通过细胞毒性分析,证明了 Mn~(2+)-CNPs有很好的生物相容性。在小鼠体内注射纳米材料15分钟后肿瘤部位的成像强度增加了 64%,有很强的肿瘤成像增强效果。通过血浆和细胞降解实验,证明了Mn~(2+)-CNPs可被生物降解。因此,Mn~(2+)-CNPs在临床上对肿瘤的诊断和治疗中有着巨大的应用潜力。
[Abstract]:Cancer is a malignant disease threatening human health. Accurate diagnosis and treatment of cancer is very important to improve the cure rate of cancer. Magnetic resonance imaging (NMR) is a commonly used diagnostic technique with the advantages of radiation-free, high resolution, high accuracy and multi-parameter imaging. In order to improve the contrast, magnetic resonance imaging contrast agent is needed in the process of nuclear magnetic imaging. Photothermal therapy is a new method for cancer treatment, which has the advantages of high accuracy and less damage. It is very important to have a photothermal therapy agent with high photothermal conversion efficiency in photothermal therapy. With the development of nanomaterials, the applications of nanomaterials in biomedicine have been extensively studied due to their unique optical, magnetic and electrical properties. Magnetic resonance imaging contrast agents can be divided into T1 and T2, manganese nanomaterials as contrast agent, can effectively improve the T1 imaging effect. Photothermal agents generally include dyestuffs, precious metal materials, carbon materials and semiconductor materials. Multifunctional nanomaterials integrated with diagnosis and treatment have been widely studied. However, the toxicity and metabolism of nanomaterials in vivo are the major obstacles to the clinical use of nanomaterials, and have been concerned by people all the time. In this paper, from the point of view of food science, using food caramel reaction as a synthetic method, we use glucose to synthesize biocompatible and biodegradable caramel nanomaterials. A large number of functional groups on the surface of caramel carbon nanoparticles can form manganese carbon nanomaterials for nuclear magnetic resonance imaging and photothermal therapy of cancer. The details are summarized as follows: 1. We synthesized the biocompatible carbon caramel nanoparticles loaded with ultrathin mn _ 3O _ 4 nanocomposites by self-sacrificial redox method, which were used in the study of T1 contrast agent and T _ 1-weighted imaging of liver nuclear magnetic imaging. The nanomaterials can be swallowed by Kupffer cells and have a high relaxation rate. We have studied the synthesis of Mn304-CNPs and the relaxation rate of mn _ 3O _ 4-CNPs as the characteristic of magnetic resonance imaging. The relaxation rate of 11.6mM-1s-1 is nearly three times that of the gadolinium chelate used in clinic. The liver signal of mice was enhanced by 50.1% 4 h after injection of nano material. The content of manganese in mice was equal to that before injection for 48 hours. Therefore, mn _ 3O _ 4-CNPs can be used as contrast-agent of liver nuclear magnetic imaging. We synthesized biodegradable, pH responsive carbon nanoparticles loaded with Mn~(2 / Mn-MN ~ (2 +) -CNPs) for nuclear magnetic resonance imaging and photothermal therapy of tumor by ion adsorption and coordination. The photothermal properties of the nanomaterials, such as. MNO _ 2 ~ (2 +) -CNPs, have good photothermal effect after laser irradiation. Under the condition of pH 5, the release rate of manganese ion reached 45%, which indicated that there was a pH response effect. The biocompatibility of Mn~(2 was proved by cytotoxicity analysis. The imaging intensity of tumor site was increased by 64% after 15 minutes of injection of nanomaterials in mice, and the enhancement effect of tumor imaging was very strong. The biodegradation of Mn~(2 was demonstrated by plasma and cell degradation experiments. Therefore, MNS-CNPs have great potential in the diagnosis and treatment of tumor.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R73-3;TB383.1

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