核壳结构铁酸盐纳米立方块的制备及其靶向磁热疗与化疗协同治疗研究

发布时间：2018-01-03 18:26

本文关键词：核壳结构铁酸盐纳米立方块的制备及其靶向磁热疗与化疗协同治疗研究　出处：《上海师范大学》2015年硕士论文　论文类型：学位论文

【摘要】：当前,癌症治疗的主要方法有手术、放疗、化疗,取得了一些成果也还存在很多问题。为了进一步提高癌症治疗水平,近来发现的新型治疗技术有光热治疗、光动力治疗、磁热疗、栓塞疗法、新型药物化疗和基因疗法等。其中磁热疗技术由于无创或微创,不存在组织穿透问题,越来越备受关注。磁热治疗技术是利用磁热效应,以高温杀死病变组织细胞。即放置在高频交变磁场中的磁热材料,会产生大量的热,能迅速提高材料附近的温度,使病变细胞死亡。其特点有准确定位,杀死病变细胞或组织,而在众多的治疗技术中,磁热疗越来越备受关注。化学疗法是利用能治疗疾病,但不导致病人死亡的化学物质治疗某种疾病,有一定的治疗效果,但是毒副作用大。新型药物通过载体将化疗药物定点运输到病变组织,再控制缓慢释放,可以减小药物用量,从而大大降低毒副作用。经过近几年的发展,报道有多模式治疗法。比如将光热疗和化疗结合,光热疗和光动力疗法结合、将光动力疗法和化疗结合、磁热疗和光热疗结合等。这些双模式的治疗,进一步提高了癌症治疗的效果。相对于单一治疗,多模式治疗集单一模式的优点于一身,甚至具有协同作用,其治疗效果较大提高了。例如将光热和化疗结合在一起,化学药物能降低癌细胞对热的耐受性,再施加光热,从而能高效杀死癌细胞。本文研究了一种具有磁热和化疗功能的铁酸盐复合材料纳米粒子。首先通过高温热解的方法制备了(Zn0.4Co0.6)Fe2O4@(Zn0.4Mn0.6)Fe2O4纳米立方块,该材料具有较大的饱和磁化率,其产热率(Specific adsorption rate-SAR,即单位质量将其他能量转换成热能的量,单位为w/g)比较大,适合做磁热材料。另外,经过化学修饰,材料接有PEG,在磷酸缓冲溶液、血清中具有较好的分散性,较小的毒副作用,较好生物相容性。材料进一步修饰透明质酸(HA)和阿霉素(DOX),使得其能靶向宫颈癌细胞(He La),DOX在癌细胞中释放,具有化疗作用。第一章总结概括了肿瘤的疗法和磁热疗法的原理及特点,概述了磁热材料的制备、结构、性质和应用。最后概括总结了肿瘤诊断和治疗上最新的研究方向,并提出了本论文的研究设想。第二章介绍了一种MNPs-PEG/HA-DOX的纳米复合材料的制备及其靶向磁热疗化疗协同治疗的研究。实验采用高热热解法,种子法合成了核壳结构铁酸盐纳米立方块。然后对纳米粒子进行了改性,修饰PEG、HA和DOX。通过一系列电镜和光谱等表征手段,对MNPs-PEG/HA-DOX纳米材料的结构和性质进行了分析。证明了成功制备了构想的材料。接着进一步验证材料磁热性能、药物输送特性和核磁共振造影效果。最后在细胞水平评价了磁性纳米粒子的协同治疗效果。并且在活体内证明了其磁热和核磁共振成像效果。第三章对本文的主要结论进行了总结整理,并对以多功能协同治疗磁性纳米复合材料的的应用前景加以展望。
[Abstract]:At present, the main methods of cancer treatment are surgery, radiotherapy, chemotherapy, and there are still many problems. In order to further improve the level of cancer treatment, the recently discovered new treatment technology is photothermal therapy. Photodynamic therapy, magnetothermic therapy, embolization therapy, new drug chemotherapy and gene therapy, etc., among them, there is no tissue penetration problem due to non-invasive or minimally invasive magnetothermal therapy. More and more attention has been paid to magnetocaloric therapy, which uses magnetocaloric effect to kill diseased tissue and cells in high temperature. That is, magnetocaloric material placed in high frequency alternating magnetic field will produce a lot of heat. It can rapidly raise the temperature near the material and make the diseased cells die. It has the characteristics of accurate location, killing the diseased cells or tissues, and in many therapeutic techniques. Magnetic hyperthermia is becoming more and more concerned. Chemotherapy is the use of chemicals that can treat diseases, but do not cause death to treat a disease, and has a certain therapeutic effect. But the toxic side effect is big. The new drug carries the chemotherapeutic drug to the pathological tissue through the carrier, then controls the slow release, can reduce the drug dosage, thus reduces the toxic side effect greatly. After the recent several years' development. There are multiple modes of treatment, such as combination of photohyperthermia and chemotherapy, photohyperthermia and photodynamic therapy, combination of photodynamic therapy and chemotherapy, magnetic hyperthermia and photohyperthermia. Compared with single treatment, multi-mode therapy has the advantages of single mode, and even has synergistic effect. For example, by combining photoheat with chemotherapy, chemical drugs can reduce the tolerance of cancer cells to heat and then apply photoheat. In this paper, a kind of ferrate composite nanoparticles with magnetocaloric and chemotherapeutic functions was studied. Firstly, Zn0.4Co0.6was prepared by pyrolysis at high temperature. Fe2O4@(Zn0.4Mn0.6)Fe2O4 nano-square. The material has high saturation magnetic susceptibility, and its heat yield is equal to that of specific adsorption rate-SAR, that is, the amount of other energy converted into heat energy per unit mass. In addition, after chemical modification, the material has PEG, in phosphoric acid buffer solution, serum has better dispersion, less toxic side effects. Better biocompatibility. The material further modified hyaluronic acid (HA) and adriamycin (DOXN), so that it can target cervical cancer cells he Lahuo DOX release in cancer cells. The first chapter summarizes the principles and characteristics of tumor therapy and magnetothermal therapy, and summarizes the preparation and structure of magnetocaloric materials. Properties and applications. Finally, the latest research directions in the diagnosis and treatment of cancer were summarized. In the second chapter, we introduce the preparation of a MNPs-PEG/HA-DOX nanocomposite and the research of the chemotherapeutic synergistic therapy of targeted magnetothermic therapy. Hyperthermia was used in the experiment. Solution. The core-shell ferrate nanorods were synthesized by seed method. Then the nanoparticles were modified to modify PEGN HA and DOX. The nanoparticles were characterized by a series of electron microscopy and spectra. The structure and properties of MNPs-PEG/HA-DOX nanomaterials were analyzed. It was proved that the proposed materials were successfully prepared, and the magnetocaloric properties of the materials were further verified. Finally, the cooperative therapeutic effect of magnetic nanoparticles was evaluated at the cell level, and the results of magnetocalorimetry and magnetic resonance imaging were proved in vivo. The conclusion is summarized. The application prospect of multifunctional cooperative treatment of magnetic nanocomposites is also prospected.
【学位授予单位】：上海师范大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TQ138.11;TB383.1

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