三元金属氧化物纳米材料制备及其在糖尿病检测和治疗的应用研究

发布时间：2018-01-10 23:10

本文关键词：三元金属氧化物纳米材料制备及其在糖尿病检测和治疗的应用研究　出处：《浙江大学》2017年博士论文　论文类型：学位论文

【摘要】：糖尿病已经成为21世纪全球最重要的健康问题之一。糖尿病的日常血糖管理关乎着数亿患者的正常生活。连续血糖监测仪正成为糖尿病慢病管理的重要手段之一,它可以实时、准确地探测血糖浓度,并控制胰岛素注射剂量。为了更好的实现这些目标,需要研究制备具有更高灵敏度,更快响应速度,更大线性范围,更高稳定性的葡萄糖生物传感器,同时研究制备可用于糖尿病治疗相关药物负载和可控释放的载体。为此,我们做了如下三个方面的研究工作:(1)新材料的制备研究。从新材料的选择和制备方法入手,我们制备了三元金属氧化物纳米材料,包括KNbO3、LiNbO3、NiCo2O4和CoFe2O4纳米材料,并利用金纳米颗粒修饰提高了三元金属氧化物基生物传感器的性能。首先,我们用水热法制备了 KNbO3纳米针,并将其应用于有酶双氧水的探测。KNbO3纳米针的钙钛矿非中心对称结构可以有效促进载流子的分离。通过表面铌离子的eg轨道和表面吸附氧中间体之间形成的σ键,可以实现KNbO3和辣根过氧化物酶对双氧水的共催化。基于KNbO3纳米针构建的有酶双氧水生物传感器的探测灵敏度达到了 750μA·mM-1·cm-2,线性范围为0.04～6mM,并且可以在1～2 s内实现对双氧水的快速响应。在KNbO3纳米针上修饰金纳米颗粒之后,金纳米颗粒能有效促进电荷分离和电子传递。制备得到的无酶双氧水生物传感器探测灵敏度为318.2μA·mM-1·cm-2,这相比于KNbO3纳米针无酶双氧水生物传感器探测灵敏度提升了 64%。其次,我们用熔融盐法和生物模板法分别制备得到了 LiNbO3纳米颗粒和纳米管,并将其应用于有酶葡萄糖生物传感器。LiNbO3具有的最大自极化强度,可以更好地促进载流子的分离。用生物模板法制备的LiNbO3纳米管相比于LiNbO3纳米颗粒具有更多的比表面积,介孔和褶皱,有利于酶分子的固定,为保持酶活性提供了合适的微环境,同时其一维管状结构也有利于反应物和酶分子之间的充分接触,因此基于LiNbO3纳米管构建的有酶葡萄糖生物传感器具有更好的性能,其探测灵敏度达到了 52.4 μA·mM-1·cm-2,这相比于铌酸锂纳米颗粒提升了 86.5%。同时其线性范围为0.3～3.3 mM,并可以在2s内实现葡萄糖的快速响应。再次,我们用水热法在钛片衬底上合成了 NiCo2O4纳米材料,并将其应用于无酶的葡萄糖生物传感器。随着水热温度的提高,NiCo2O4纳米材料形貌从纳米片逐渐向纳米线转变,分别探测它们的葡萄糖生物传感器性能,发现纳米片/纳米线复合结构的NiCo2O4具有最大的葡萄糖探测灵敏度,达到了惊人的1530μA·mM-1·cm-2。在此基础上,提高制备过程中F-离子的加入浓度,以此制备的葡萄糖生物传感器的探测灵敏度达到了 2387 μA·mM-1·cm-2,比之前足足提升了1.23倍。在NiCo2O4纳米片上修饰了金纳米颗粒之后,制备得到无酶葡萄糖生物传感器的探测灵敏度为2979 μA·mM-1·cm-2,这相比NiCo2O4纳米片葡萄糖生物传感器的探测灵敏度又提升了 24.8%。最后,我们利用水热法合成了中空CoFe2O4多孔微球,并将其应用于色比葡萄糖生物传感器。通过反应时间控制的系列实验,中空CoFe2O4多孔微球的生长过程可以解释为原位溶解再结晶。利用TMB显色剂在652 nm处的可见光吸收峰强的变化情况,我们实现了 CoFe2O4对葡萄糖的色比探测,线性范围为0.67～6.67 mM。(2)传感器集成化研究。我们结合光转换,能量储存和生物传感制备得到NiCo2O4/SnO2全固态自驱动的葡萄糖生物传感器。在光照条件下,光电流随着葡萄糖浓度增大而线性减小,其检测线性范围为2～40mM。在无光照条件下,利用储能电极中储存的化学能可以氧化葡萄糖,开路电压和葡萄糖浓度变化呈现很好的线性关系,其检测线性范围为2～12 mM。(3)药物负载和释放研究。我们制备的中空CoFe2O4多孔微球具有很高的比表面积,它的药物负载效率为88.6%,每克CoFe2O4微球可以负载118.1 mg DOX药物。在酸性pH值下,DOX负载的CoFe2O4微球具有更快的药物释放速率和更大的累积药物释放量。CoFe2O4微球具有较强的磁性,可以在交变磁场下实现对药物的可控释放。随着交变磁场频率和强度的增加,相同时间内,CoFe2O4药物载体的累积药物释放量增加。前期CoFe2O4药物载体的研究工作为今后胰岛素负载和释放的研究开展建立了基础。
[Abstract]:Diabetes has become one of the most important global health problems in twenty-first Century. The daily blood glucose management of diabetes related to the normal life of hundreds of millions of patients. Continuous glucose monitoring is becoming an important means of managing chronic disease of diabetes, it can real-time, accurate detection and control of blood glucose, insulin dose. In order to achieve these goals better, need to study the preparation has higher sensitivity, faster response speed, wider linear range, more glucose biosensor with high stability, and can be used for the preparation of vector treatment of diabetes related drug release and controllable loads. Therefore, we do research in the following three aspects: (1) the preparation of new materials. Starting from the selection and preparation of new material method, we prepared three yuan of metal oxide nano materials were prepared, including KNbO3, LiNbO3, NiCo2O4 and CoFe2O4 nano materials, and The performance of three yuan of metal oxide based biosensor improved by gold nanoparticles. Firstly, we use water thermal method of KNbO3 nano needle was prepared, and its application in separation of hydrogen peroxide enzyme detection.KNbO3 nano needle perovskite non centrosymmetric structure can effectively promote the carrier. The bonding between the surface formed by niobium ion eg orbitals and surface adsorbed oxygen intermediates, can achieve KNbO3 and horseradish peroxidase on the catalytic hydrogen peroxide. The detection sensitivity of KNbO3 nano needle to build a hydrogen peroxide biosensor enzyme reached 750 A - mM-1 - cm-2 based on the linear range of 0.04 ~ 6mM, and can be in 1 ~ 2 s in the fast response the hydrogen peroxide. After modified gold nanoparticles in KNbO3 nano needles, gold nanoparticles can effectively promote the electron transfer and charge separation. Non enzymatic hydrogen peroxide biosensor prepared The detection sensitivity of 318.2 A - mM-1 - cm-2, which compared to the KNbO3 nano needle enzyme biosensor of hydrogen peroxide enhance the detection sensitivity of 64%.. Secondly, we use molten salt method and biological template method respectively to prepare LiNbO3 nanoparticles and nanotubes, and applied to the maximum self polarization glucose biological enzyme.LiNbO3 has a sensor, can better promote the separation of carriers. Compared with biological template preparation of LiNbO3 nanotubes in LiNbO3 nano particles have more surface area, mesoporous and fold, in favor of the enzyme molecules fixed, provide a suitable microenvironment for maintaining enzyme activity at the same time, it also has one-dimensional tubular structure for full contact between the reactants and enzyme molecules, so based on the performance of the LiNbO3 nanotubes construction of glucose biosensor has better, its detection sensitivity reached 52.4 A - mM-1 Cm-2, this is compared to lithium niobate nanoparticles to enhance the 86.5%. and the linear range was 0.3 ~ 3.3 mM, fast response and can achieve glucose within the 2S. Once again, our hydrothermal method NiCo2O4 synthesis of nano materials on titanium substrate, and its application in glucose biosensor with free enzyme. The increase of hydrothermal temperature, morphology of NiCo2O4 nano materials from nanosheets nanowires to gradually change, respectively, the detection performance of the glucose biosensor are found, nanosheets nanowires of NiCo2O4 have the maximum glucose detection sensitivity, a staggering 1530 A - mM-1 - cm-2. on the basis of this, increasing the concentration of added F- ion in the preparation process, detection sensitivity to glucose biosensor system by up to 2387 A - mM-1 - cm-2, for up to 1.23 times than before. The nano NiCo2O4 modified gold Nano particles were prepared after the detection sensitivity of non enzymatic glucose biosensor is 2979 A - mM-1 - cm-2, compared the detection sensitivity of nano NiCo2O4 glucose biosensor and enhance the 24.8%. finally, we use the hydrothermal method of hollow porous CoFe2O4 microspheres were synthesized, and its application in glucose biosensor is through. A series of experimental control of the reaction time, the growth process of hollow porous CoFe2O4 microspheres can be explained by in situ dissolution recrystallization. Measured by TMB reagent at 652 nm visible light absorption peak intensity, we implement CoFe2O4 on glucose is detected, the linear range was 0.67 ~ 6.67 mM. (2) of sensor integration. We combine optical conversion, energy storage and biosensor prepared by glucose biosensor NiCo2O4/SnO2 full solid self driving. Under the condition of illumination, the light with the current With the increase of glucose concentration decreases linearly, the linear range of detection was 2 ~ 40mM. in no light condition, the storage electrode chemical energy stored in the oxidation of glucose can change, open circuit voltage and glucose concentration showed a good linear relationship, the linear range of detection was 2~12 mM. (3) and the release of drug loading we prepared hollow porous CoFe2O4 microspheres prepared with high specific surface area, its drug loading efficiency was 88.6%, per gram of CoFe2O4 microspheres can load 118.1 mg DOX drugs. In acidic pH, CoFe2O4 microspheres DOX load faster drug release rate and cumulative drug release more.CoFe2O4 microspheres with strong magnetism can be controlled on the release of the drug in alternating magnetic field. With the increase of magnetic field intensity and frequency, the same time, the cumulative drug CoFe2O4 drug carrier increased release. The research work of phase CoFe2O4 drug carrier has established the foundation for the study of insulin load and release in the future.

【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R587.1;TB383.1

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