基于氧化石墨烯的纳米杂化材料在肿瘤多模成像和治疗中的应用

发布时间：2018-01-03 10:06

本文关键词：基于氧化石墨烯的纳米杂化材料在肿瘤多模成像和治疗中的应用　出处：《上海师范大学》2017年硕士论文　论文类型：学位论文

【摘要】：石墨烯(Graphene)是一种由碳原子构成的新型材料,是由碳原子以sp2杂化轨道组成六角型呈蜂巢晶格平面结构、只有一个碳原子厚度的二维材料。氧化石墨烯(Graphene Oxide)是石墨烯的一种重要的衍生物,也被称为功能化的石墨烯。它的结构与石墨烯大体相同,只是在二维基面上连有一些官能团。氧化石墨烯具有很大的比表面积和丰富的表面缺陷,无机纳米颗粒可以通过原位生长或后修饰负载到氧化石墨烯表面。通过良好的表面功能化修饰可提高GO在生物体内的稳定性以及可控性,从而可以获得良好生物相容性的基于氧化石墨烯的纳米杂化材料。氧化石墨烯纳米杂化材料不仅可用于肿瘤的光热治疗和作为载体进行药物和基因输送,还可被用作造影剂应用在生物多模式成像中,包括CT成像、磁共振成像(MRI)以及光声成像(PAI)等。目前,己经有大量文章报道了关于GO及其衍生物在生物医学方面的广泛应用。本论文主要研究在氧化石墨烯表面负载Mn WO_4或Bi_2Se_3纳米粒子,并通过一锅法在纳米材料表面修饰改善生物相容性的聚乙二醇(PEG)或聚乙烯吡咯烷酮(PVP)进行改性。通过π-π相互作用和静电相互作用得到负载盐酸阿霉素(DOX)的氧化石墨烯基纳米杂化材料,可以被应用在光热治疗或光热/药物协同治疗。第一章综述了氧化石墨烯的结构、性质、制备方法、表面功能化修饰以及其在生物成像和肿瘤治疗上的应用。第二章研究了GO/Mn WO_4/PEG纳米杂化材料的制备、表征以及其在细胞、活体中的生物成像和治疗方面的应用。通过高温加热一步合成的GO/MnWO_4/PEG纳米杂化材料,具有良好的形貌、较小的尺寸和良好的分散性。溶液水平表征结果表明,材料在近红外有较强吸收,在激光照射下有良好的升温效果。GO/Mn WO_4/PEG纳米杂化材料表面负载抗癌药物DOX后,在酸性环境中药物释放较多,并且在光热条件下,其药物释放的能力会得到一定增强。同时,GO/MnWO_4/PEG纳米杂化材料在溶液水平表现出良好的MRI/CT/PA造影性能,并且在相应的活体成像上也取得了良好的造影效果。GO/MnWO_4/PEG纳米杂化材料在体外实验中表现出了良好的生物相容性,并且对4T1细胞有较好的光热/药物杀死效果。基于材料良好的生物相容性和体外治疗效果,将GO/MnWO_4/PEG纳米杂化材料应用在活体荷瘤小鼠的肿瘤治疗上,在治疗期间,肿瘤基本被抑制,取得了良好的光热/药物协同治疗效果。因此,GO/MnWO_4/PEG纳米杂化材料可以应用于生物体内的多模成像和光热/药物协同治疗。第三章研究了GO/Bi_2Se_3/PVP纳米杂化材料在生物体内的CT/PA成像和肿瘤的光热治疗。通过尾静脉向荷瘤小鼠体内注射该材料,然后对小鼠进行CT成像扫描,可在小鼠肿瘤部位观察到一定的成像效果。GO/Bi_2Se_3/PVP纳米材料在溶液水平的光声成像效果良好,可以观察到随着材料溶液浓度增大,材料成像对比度增强,后将其应用于活体荷瘤小鼠的光声成像并取得了良好的成像效果,说明该材料可作为CT/PA双模式成像造影剂。同时,研究了GO/Bi_2Se_3/PVP纳米杂化材料对荷瘤小鼠肿瘤的光热消融效果,得到了较好的光热治疗效果。因此,GO/Bi_2Se_3/PVP纳米杂化材料可以作为生物体内的CT/PA成像造影剂和癌症光热治疗剂。第四章总结了本论文中的各项数据和结果,并对基于GO的纳米杂化材料在生物医药上的应用进行展望。
[Abstract]:Shi Moxi (Graphene) is a kind of new material composed of carbon atoms, is made of carbon atoms to SP2 hybrid orbitals consisting of six angle type honeycomb lattice plane structure, the two-dimensional material is only one carbon atom. The thickness of graphene oxide (Graphene Oxide) is a kind of important graphene derivatives, also called graphite as a function of the graphene and graphene structure. It is roughly the same, only in the two-dimensional surface with some functional groups. The graphene oxide has large surface area and abundant surface defects, inorganic nano particles can be obtained by in situ growth or after modification of the load to the surface of graphene oxide. By surface modification function can improve the stability of GO in organisms and controllability, which can obtain good biocompatibility of nano hybrid materials based on graphene. The graphene oxide nano hybrid materials can be used not only to swell Photothermal therapy of tumor and as a carrier of drug and gene delivery, can also be used as contrast agent used in biological pattern imaging, including CT imaging, magnetic resonance imaging (MRI) and photoacoustic imaging (PAI). At present, there are a large number of articles have been reported on the application of GO and its derivatives in biomedicine the. This paper mainly studies the load Mn WO_4 or Bi_2Se_3 nanoparticles on the surface of graphene oxide and modified by one pot method, improve the biocompatibility of the nano materials in the surface of polyethylene glycol (PEG) or polyvinylpyrrolidone (PVP) was modified by tt-tt and electrostatic interactions are supported (doxorubicin hydrochloride DOX) graphene oxide based nano hybrid materials can be used in photothermal therapy or thermal / drug therapy. The first chapter summarizes the collaborative structure, graphene oxide, preparation method, surface modification And its application in biological imaging and tumor therapy. The second chapter studies the preparation of GO/Mn WO_4/PEG nano hybrid materials, characterization and its application in living cells, biological imaging and therapy. By heating one step synthesis of GO/MnWO_4/PEG nano hybrid materials, has good appearance, small size and good the dispersion. The characterization results show that the level of solution, material has strong absorption in the near infrared, under the laser irradiation load anticancer drug DOX good heating effect of.GO/Mn WO_4/PEG nano hybrid material surface, in the acidic environment of drug release more, and in the thermal conditions, the drug release will be enhanced. At the same time, GO/MnWO_4/PEG nano hybrid materials in solution MRI/CT/PA contrast levels showed a good performance, and the corresponding in vivo imaging has achieved favorable angiography effect. GO/MnWO_4/PEG nano hybrid materials in vitro showed good biocompatibility, and good thermal / drugs killing effect on 4T1 cells in vitro. The compatibility and treatment effect of good biological material based on tumor GO/MnWO_4/PEG nano hybrid materials used in the in vivo tumor bearing mice in the treatment, during the treatment of cancer is suppressed, and achieved good thermal / drug synergistic therapeutic effect. Therefore, the multimode imaging and photothermal / GO/MnWO_4/PEG nano hybrid materials can be used in the in vivo drug synergistic treatment. The third chapter studies the thermal treatment of GO/Bi_2Se_3/PVP nano hybrid materials in vivo CT/PA imaging and tumor. Through tail vein injection to mice the material, then the CT imaging of mice can be observed in mouse tumor imaging effect of.GO/Bi_2Se_3/PVP nano materials to a certain The material of photoacoustic imaging effect in the solution level is good, can be observed with the material concentration increased, the material image contrast enhancement, after its application in tumor bearing mice in vivo photoacoustic imaging and achieved good imaging effect, indicating that the material can be used as a CT/PA dual mode imaging contrast agent. At the same time, study thermal GO/Bi_2Se_3/PVP nano hybrid materials of tumor ablation effect, obtained better effect of photothermal therapy. Therefore, GO/Bi_2Se_3/PVP nano hybrid materials can be used as the organism CT/PA imaging contrast agent and cancer photothermal therapeutic agent. The fourth chapter summarizes the data and results presented in this paper, and the prospect of application in biology medicine on the nano hybrid materials based on GO.

【学位授予单位】：上海师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R730;TB383.1

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