本文選題：納米氧化石墨烯 + 腫瘤�。� 參考：《上海師范大學(xué)》2015年碩士論文

【摘要】：納米氧化石墨烯,即石墨烯的氧化衍生物,作為一種新型二維的碳納米材料,具有超大的比表面積和優(yōu)異的光熱效果等性質(zhì),已成為納米醫(yī)學(xué)領(lǐng)域中備受關(guān)注的研究熱點。納米氧化石墨烯含有大量的活性化學(xué)基團(tuán),比如羧基、羰基、羥基和環(huán)氧基等,既容易對其進(jìn)行生物化學(xué)功能化,又使其具有很好的生物相容性,因此在生物醫(yī)學(xué)領(lǐng)域中表現(xiàn)出很強(qiáng)的應(yīng)用潛能。本論文的主要內(nèi)容:采用改進(jìn)后的Hummers法制備得到不同尺寸的納米氧化石墨烯,隨后在其表面共價修飾聚乙二醇和熒光分子Cy5.5,通過體外細(xì)胞實驗得到最優(yōu)化的納米氧化石墨烯。然后在最優(yōu)化納米氧化石墨烯表面共價修飾靶向分子葉酸(FA),并且分別標(biāo)記上核素125I以及熒光分子Cy5.5,形成核醫(yī)學(xué)分子影像探針(125I-n GO-PEG-FA)及光學(xué)分子影像探針(n GO-PEG-Cy5.5-FA)。通過活體腫瘤模型的光學(xué)和核素顯像,研究探針對腫瘤的靶向性和體內(nèi)生物學(xué)性質(zhì),并用于腫瘤靶向性核素及光學(xué)分子影像的研究。全文共分為三章。第一章為緒論即綜述。該章主要概括了石墨烯的制備、性質(zhì)、結(jié)構(gòu)和表面功能化的方法以及石墨烯的衍生物氧化石墨烯在生物體中的應(yīng)用,同時介紹了納米氧化石墨烯在核素成像和光學(xué)成像方面的應(yīng)用,最后提出了本論文的研究設(shè)想。第二章為本論文核心內(nèi)容即實驗研究。首先,我們采用改進(jìn)后的Hummers法制備得到不同尺寸的納米氧化石墨烯,隨后在其表面共價修飾聚乙二醇(PEG),通過體外細(xì)胞毒性實驗、基于熒光分子Cy5.5標(biāo)記的細(xì)胞激光共聚焦實驗得到最優(yōu)化的氧化石墨烯,進(jìn)一步研究其細(xì)胞及活體中的應(yīng)用。然后,通過在最優(yōu)化納米氧化石墨烯表面分別連接靶向分子葉酸(FA)、熒光染料分子Cy5.5和核素125I,得到葉酸靶向性功能納米材料。體外實驗表明,材料具有低的細(xì)胞毒性,激光共聚焦實驗表明材料對高表達(dá)葉酸受體的4T1細(xì)胞具有顯著的靶向作用,對A549沒有明顯靶向性。經(jīng)尾靜脈分別將靶向材料n GO-PEG-Cy5.5-FA和125I-n GO-PEG-FA注射進(jìn)荷瘤鼠體內(nèi),對其分別進(jìn)行活體小動物SPECT/CT和光學(xué)顯像,發(fā)現(xiàn)材料n GO-PEG-Cy5.5-FA和125I-n GO-PEG-FA在4T1腫瘤內(nèi)高度攝取,而封閉組的4T1腫瘤的攝取不明顯,表明該納米材料具有腫瘤葉酸受體靶向性。通過組織分布(HE染色)研究了該材料的小鼠體內(nèi)毒性,結(jié)果表明,納米材料沒有表現(xiàn)出明顯毒性,在活體小動物體內(nèi)有較好的生物相容性。因此,該葉酸功能化納米氧化石墨烯具有顯著的葉酸受體靶向性,是葉酸受體陽性腫瘤的多模式分子影像探針的潛在的理想納米載體,在癌癥診斷和治療一體化應(yīng)用方面具有潛在的應(yīng)用前景。第三章為總結(jié)與展望,主要是將本論文所得到的結(jié)果進(jìn)行了歸納總結(jié),并且展望了納米氧化石墨烯在生物醫(yī)學(xué)領(lǐng)域的應(yīng)用前景。
[Abstract]:Nanocrystalline graphene oxide, the oxidation derivative of graphene, as a new two-dimensional carbon nano-material, has the properties of super large specific surface area and excellent photothermal effect, and has become a hot research topic in the field of nano-medicine. Nano graphene oxide contains a large number of active chemical groups, such as carboxyl, carbonyl, hydroxyl and epoxide groups, which are easy to be biochemically functionalized and have good biocompatibility. Therefore, in the field of biomedicine has shown a strong potential for application. The main contents of this thesis are as follows: Nano-graphene oxide with different sizes was prepared by modified Hummers method, and then covalently modified with polyethylene glycol and fluorescent molecule Cy5.5 on its surface. The optimized nano-graphene oxide was obtained by cell experiments in vitro. Then the target molecule folate was covalently modified on the surface of graphene oxide and labeled with radionuclide 125I and fluorescent molecule Cy5.5. the molecular imaging probe of nuclear medicine was formed by 125I-n GO-PEG-FAA and the optical molecular image probe (n GO-PEG-Cy5.5-FAA). Optical and radionuclide imaging of tumor models in vivo was used to study the tumor targeting and biological properties of the probe and to study the tumor targeting radionuclide and optical molecular imaging. The full text is divided into three chapters. The first chapter is the introduction. This chapter summarizes the preparation, properties, structure and surface functionalization of graphene and the application of graphene oxide, a derivative of graphene, in living organisms. At the same time, the applications of nano-graphene oxide in radionuclide imaging and optical imaging are introduced. The second chapter is the core content of this paper, that is, experimental research. Firstly, we prepared different sizes of graphene oxide by modified Hummers method, and then covalently modified PEGN on its surface. The optimized graphene oxide was obtained by laser confocal method based on fluorescent molecular Cy5.5 labeling, and its applications in cells and in vivo were further studied. Then, folic acid targeted functional nanomaterials were obtained by joining the target molecule folate, fluorescent dye molecule Cy5.5 and nuclide 125i on the optimized surface of graphene oxide. In vitro experiments showed that the materials had low cytotoxicity, and laser confocal microscopy showed that the materials had a significant targeting effect on 4T1 cells with high folate receptor expression, but not on A549 cells. The target materials, n GO-PEG-Cy5.5-FA and 125I-n GO-PEG-FA, were injected into the tumor bearing mice through the tail vein respectively. The SPECT/CT and optical imaging of small animals were performed respectively. It was found that the material n GO-PEG-Cy5.5-FA and 125I-n GO-PEG-FA were highly ingested in 4T1 tumor, but the 4T1 tumor uptake was not obvious in the blocking group. The results show that the nano-material has tumor folic acid receptor targeting. The toxicity of the material in mice was studied by tissue distribution HE staining. The results showed that the nano-material had no obvious toxicity and had good biocompatibility in vivo small animals. Therefore, the folic acid functionalized graphene oxide has significant folic acid receptor targeting and is a potential ideal nanometer carrier for multimode molecular imaging probes of folate receptor-positive tumors. It has a potential application prospect in the integrated application of cancer diagnosis and treatment. The third chapter is the summary and prospect, mainly summarizes the results obtained in this paper, and looks forward to the application prospect of nano-graphene oxide in biomedical field.
【學(xué)位授予單位】：上海師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：TQ127.11;TB383.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 徐秀娟;秦金貴;李振;;石墨烯研究進(jìn)展[J];化學(xué)進(jìn)展;2009年12期

2 張振華;α-氨基酸與茚三酮顯色反應(yīng)影響因素的探討[J];邵陽高等�？茖W(xué)校學(xué)報;2000年01期

，

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