基于导电聚合膜的抗肿瘤药物分子印迹传感器的研究

发布时间：2018-08-31 16:16

【摘要】：社会经济的不断进步与发展使人类的生活水平日益提高的同时,相应的也凸显出诸多社会性问题,诸如人口老龄化的加剧、生态环境的破坏、食品安全问题及现代人不健康的生活方式等,致使罹患癌症的人数不断增多。近年来,我国肿瘤发病率不断上升,其死亡率也已高出世界水平,已成为必须高度重视的社会性问题。目前,临床上很多癌症的治疗多依赖于抗肿瘤药物,但它在人体内的存在量直接影响人体健康状况,因此构建一种能快速、准确检测该药物的方法对其相关疾病的诊断大有益处。本文以盐酸阿霉素、长春新碱和左氧氟沙星作为主要研究目标,利用分子印迹技术对研究目标的选择性识别,将分子印迹技术与电化学传感器有效结合,通过自组装、电化学聚合等方法在基体电极表面制备导电性良好且有生物相容性的纳米复合膜,构建一系列基于导电聚合膜的抗肿瘤药物分子印迹传感器,并将电化学技术作为主要测定手段对其各项性能进行研究讨论。纳米复合膜比表面积大、导电能力强的性能可显著提高所构建传感器的电流响应、对目标分子的有效识别能力以及检测的灵敏度。优化实验条件后,将所研制传感器实用于生活,考察其实用价值,有望构建一种能对该药物进行快速、灵敏、准确识别和检测的方法。主要研究内容如下:1.以3,4-乙烯二氧噻吩(EDOT)为功能单体,盐酸阿霉素(DOX)为模板分子,在基体金电极表面通过电聚合等技术制备DOX印迹敏感膜(MIPs),构建了一种可以对DOX进行选择性检测的分子印迹传感器。通过一系列电化学表征手段对所构建传感器的电化学性能进行研究。优化实验条件后,在含0.005 mol/LK3[Fe(CN)6]及0.1 mol/LKCl的PBS中测试其响应性能。实验结果表明,该传感器对DOX的检测表现有良好重现性、稳定性及选择性,其检出限(S/N=3)可达6.5×10-8 mol/L。将此传感器应用于实际生活中人体血样内DOX的测定也表现有较大的实用价值,结果较为满意。2.将长春新碱(VCR)、甲基丙烯酸(MAA)和马来松香丙烯酸乙二醇酯(EGMRA)分别作为模板分子、功能单体和交联剂,采用自由基热聚合方式合成分子印迹聚合物,并将石墨烯-金纳米粒子复合膜作为信号增敏材料电沉积至基体电极表面,由此研制一种可以选择性测定VCR的新型传感器并通过一系列电化学手段对其性能进行优化研究。实验结果表明,该研制传感器对VCR的检测范围为5.0×10-8~5.0×10-6 mol/L,相关系数为0.9952,检出限为2.6×10-8 mol/L,具有较好的选择性。将此传感器应用于药品中VCR的检测,其加标回收率为90%~120%,有一定实用价值。3.以左氧氟沙星(LVFX)为目标分子,吡咯(Py)为功能单体,采用电聚合技术在修饰有普鲁士蓝(PB)导电膜的基体电极表面研制一种可以选择性检测LVFX的分子印迹传感器。采用电化学技术对其性能进行表征,并考察所研制传感器在pH、孵化时间、洗脱剂等不同实验条件下的电化学响应变化。优化实验条件后测试所研制传感器的响应性能,结果表明该传感器对于LVFX的检测表现有良好的选择性和较宽的线性范围,且检出限达1.7×10-8 mol/L。将其用于左氧氟沙星胶囊中LVFX的分析与检测,其回收率为96%~105%,效果良好。
[Abstract]:With the continuous progress and development of social economy, the living standard of human beings is improving day by day. At the same time, many social problems are also highlighted, such as the aggravation of population aging, the destruction of ecological environment, the food safety problem and the unhealthy lifestyle of modern people. As a result, the number of cancer patients is increasing. The morbidity is rising, and the mortality rate is also higher than the world level. It has become a social problem that must be attached great importance to. At present, the treatment of many cancers in clinic mostly relies on antineoplastic drugs, but its presence in the body directly affects the health of the human body. Therefore, a rapid and accurate method for the detection of the drug phase is proposed. In this paper, doxorubicin hydrochloride, vincristine and levofloxacin were used as the main research targets. Molecular imprinting technology was used to selectively identify the research targets. Molecular imprinting technology was effectively combined with electrochemical sensors. Conductivity was prepared on the surface of substrate electrode by self-assembly and electrochemical polymerization. A series of molecularly imprinted sensors for antitumor drugs based on conductive polymeric membranes were constructed by using nanocomposite membranes with good properties and biocompatibility. After optimizing the experimental conditions, the developed sensor can be used in daily life to investigate its practical value. It is hopeful to construct a rapid, sensitive, accurate identification and detection method for the drug. The main research contents are as follows: 1. 3,4-ethylenedioxythiophene (EDOT) Doxorubicin hydrochloride (DOX) was used as a template molecule to prepare DOX imprinted sensitive membranes (MIPs) on the surface of the gold electrode. A molecular imprinted sensor for selective detection of DOX was constructed. The electrochemical performance of the sensor was optimized by a series of electrochemical characterization methods. The results show that the sensor has good reproducibility, stability and selectivity for the detection of DOX, and its detection limit (S/N=3) can reach 6.5 *10-8 mol/L. The application of the sensor to the determination of DOX in human blood samples in real life also shows that the sensor has good reproducibility, stability and selectivity. Vincristine (VCR), methacrylic acid (MAA) and maleic rosin ethylene glycol acrylate (EGMRA) were used as template molecules, functional monomers and crosslinkers respectively. Molecularly imprinted polymers were synthesized by free radical thermal polymerization, and graphene-gold nanoparticle composite films were used as signal sensitizers. A new sensor for selective determination of VCR was developed by electrodeposition on the surface of substrate electrode and its performance was optimized by a series of electrochemical methods. The experimental results show that the detection range of the sensor is 5.0 6550 This sensor has been applied to the determination of VCR in drugs with a recovery of 90%~120%. It has a certain practical value. 3. With levofloxacin (LVFX) as the target molecule and pyrrole (Py) as the functional monomer, a selective detection method was developed on the surface of the substrate electrode modified with Prussian blue (PB) conductive film by electropolymerization. Molecular imprinting sensor for measuring LVFX was developed. The performance of the sensor was characterized by electrochemical technique. The electrochemical response of the sensor under different experimental conditions, such as pH, incubation time, eluent and so on, was investigated. The method has good selectivity and wide linear range, and the detection limit is 1.7 *10-8 mol/L. The recovery of LVFX in Levofloxacin capsules is 96%~105%.
【学位授予单位】：山西师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.72;TP272;O657.1

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