功能化光电纳米材料用于肿瘤标志物检测及肿瘤细胞原位分析

发布时间：2018-02-03 23:07

  本文关键词： 肿瘤标志物 光电传感器 肿瘤细胞 纳米探针　出处：《山东师范大学》2017年硕士论文　论文类型：学位论文

【摘要】：癌症是目前社会威胁人类发展的严重疾病,也是致死率很高的疾病之一,它的发病率每年呈上升的趋势,因此,致力于癌症的治疗和预防的任务刻不容缓。癌症的早期发现与诊断是预防癌症的关键,对于癌症,是否能早期诊断与发现并采取相应的措施,直接关系到癌症患者的治愈率和生存率。临床现有的肿瘤检测方法的特异性和灵敏度很低,对癌症的早期发现仍存在很大困难,且确诊较慢,容易耽误最佳治疗时机。为了提高临床癌症诊断方法的特异性和灵敏度,我们致力于低浓度肿瘤标志物的检测和肿瘤细胞的原位成像来实现癌症的灵敏检测。本论文针对肿瘤标志物如甲胎蛋白(AFP)、micro RNA-21等,利用光电化学方法,实现了肿瘤标志物和肿瘤细胞的原位分析。本论文主要包括以下内容:1.基于石墨烯、铁卟啉、金纳米棒三元复合物开发了一种高效双猝灭电致化学发光(ECL)免疫传感器,通过具有类过氧化物酶性质的三元复合物对H2O2催化作用和金纳米棒(Au NRs)的共振能量转移产生高强度的ECL信号。这种超灵敏ECL传感策略,结合石墨烯/Au-Cd S量子点的优良ECL传感性能和双猝灭反应,实现AFP的敏感检测。2.首次合成新型石墨烯三重复合物石墨烯-铁卟啉-金纳米花(H-RGO-Au NFs),利用其优良的类过氧化物酶的催化性能及适体技术,设计一种新型电化学适体传感器,可灵敏检测白血病细胞(K562),并具有很好的选择性。3.构建信号放大型荧光纳米探针,在金颗粒(Au NPs)上修饰DNA荧光探针,探针DNA可以结合细胞内目标miRNA,引发后续的DNA酶辅助的DNA链裂解,导致荧光基团Cy5的释放,Au NPs与被释放荧光基团Cy5间的较远的距离大大减弱了之前状态的荧光猝灭效应,使Cy5产生荧光信号。此方法中一个目标物miR-21和探针结合后可以产生一系列的剪切反应,进而实现信号放大。因为mi R-21在癌细胞中是过表达的,所以这种mi R-21的纳米剪刀检测为癌细胞的检测提供了一种简单高效的方法,并且可以应用到细胞内其他基因信号放大检测和成像分析。
[Abstract]:Cancer is a serious disease threatening the development of human beings and one of the diseases with high mortality. The incidence of cancer is on the rise every year. The task of treating and preventing cancer is urgent. The early detection and diagnosis of cancer is the key to the prevention of cancer. It is directly related to the cure rate and survival rate of cancer patients. The specificity and sensitivity of the existing tumor detection methods are very low, the early detection of cancer is still very difficult, and the diagnosis of cancer is slow. In order to improve the specificity and sensitivity of clinical cancer diagnosis methods, We focus on the detection of low concentration tumor markers and in situ imaging of tumor cells to detect cancer sensitively. The in situ analysis of tumor markers and tumor cells has been achieved. In this thesis, the following contents are included: 1. Based on the ternary complexes of graphene, iron porphyrin and gold nanorods, an efficient double quenching electroluminescent chemiluminescence (ECL) immunosensor was developed. A high intensity ECL signal is generated by a ternary complex with peroxidase properties to catalyze H _ 2O _ 2 and the resonance energy transfer of gold nanorods au NRs. This super-sensitive ECL sensing strategy is developed. The excellent ECL sensing performance and double quenching reaction of graphene / Au-CdS quantum dots were studied. To realize the sensitive detection of AFP, a novel graphene triple complex, graphene, iron porphyrin-gold nano-flower, H-RGO-Au NFS was synthesized for the first time. A novel electrochemical aptamer sensor was designed by using its excellent peroxidase catalytic performance and aptamer technology. It can be used to sensitively detect K562G in leukemic cells, and has good selectivity. 3. To construct a large fluorescent nanoprobe with signal discharge and modify DNA fluorescence probe on au NPs of gold particles. The probe DNA could bind to the target miRNAs in the cell and induce the subsequent DNA chain cleavage assisted by DNA enzyme, resulting in the release of Cy5 from the fluorescent group Cy5 and the long distance between the released Cy5 group and the released fluorescence group Cy5, which greatly weakened the fluorescence quenching effect of the previous state. In this method, a target miR-21 and a probe can produce a series of shear reactions, which amplify the signal, because miR-21 is overexpressed in cancer cells. Therefore, the nanoscale scissors detection of miR-21 provides a simple and efficient method for the detection of cancer cells, and can be applied to other gene signal amplification detection and imaging analysis in cells.
【学位授予单位】：山东师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R730.4;TB383.1
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本文编号：1488605