DNA自组装纳米花的设计制备与载药及成像应用研究

发布时间：2018-07-11 15:27

本文选题：DNA + 纳米颗粒　；参考：《湖南大学》2015年硕士论文

【摘要】：DNA自组装纳米颗粒是以DNA为材料组装的纳米尺寸的结构。DNA自组装纳米颗粒拥有纳米级尺寸、均匀的颗粒粒径、可精确的控制组装和良好的生物相容性等优点。这些优点使DNA自组装纳米颗粒可广泛用于探针、生物成像或靶向给药等生物医学方面。癌症是世界头号杀手之一,2012年,全球有一千四百万人被新确诊为癌症,八百万人因为癌症而死亡。[1]癌症的高发病率和高死亡率主要是因为缺乏有效的癌症早期检测诊断技术和治疗手段。建立有效的癌症早期诊断方法和高效的靶向治疗手段是目前癌症研究领域的热点。本文将探讨如何简单、高效的构建DNA自组装纳米颗粒,并考查其在癌症的靶向给药和多色成像方面的应用。该论文的内容主要包括:第二章主要探讨了DNA纳米花的合成条件和制备方法及DNA纳米花的稳定性。DNA纳米花是高的局部浓度的DNA溶液通过液体结晶得到的,其合成需要DNA聚合酶、模板和引物DNA链的参与。DNA纳米花的合成受多个条件的影响,如DNA聚合酶的种类和浓度,DNA模板链序列,反应时间等,本章就这些条件对DNA纳米花合成的影响做了逐一探讨。此外,本章还对DNA纳米颗粒在不同温度、酶、复杂体系、药物等条件下的稳定性分别进行讨论。第三章主要介绍了DNA纳米花在靶向癌细胞给药方面的应用。本章考察DNA纳米花对两组耐药性和非耐药性癌细胞系的给药效果。内容主要包括DNA花形颗粒对靶标癌细胞结合能力的考察,对靶标癌细胞膜的穿透能力考察,对靶标癌细胞的生长抑制能力的考察等等,从多个方面评估了DNA花形颗粒对癌症给药的能力,并对比考察了它相对传统DNA纳米药物载体的优缺点。第四章主要介绍了DNA花形颗粒在细胞的多色成像应用。该章通过掺杂多种染料分子,合成了可荧光能量共振转移的多色DNA纳米花。该多色DNA纳米花可在同一激发波长下,根据不同的掺杂的荧光染料的配比,发射出不同的多色荧光。该多色DNA纳米花可在生物体系内实时监测多种目标,临床应用意义重大。
[Abstract]:DNA self-assembled nanoparticles are nano-sized structures assembled from DNA. DNA self-assembled nanoparticles have the advantages of nanoscale size, uniform particle size, accurate control assembly and good biocompatibility. These advantages make DNA self-assembled nanoparticles widely used in biomedicine such as probe biomedical imaging or targeted drug delivery. Cancer is one of the world's leading killers. In 2012, 14 million people worldwide were newly diagnosed with cancer. 8 million people died from cancer. [1] the high incidence and high mortality of cancer are mainly due to the lack of effective early detection techniques and treatments for cancer. The establishment of effective methods for early cancer diagnosis and effective targeted therapy is a hot topic in the field of cancer research. In this paper, we will discuss how to construct DNA self-assembled nanoparticles simply and efficiently, and examine their applications in cancer targeting drug delivery and polychromatic imaging. The main contents of this thesis are as follows: in the second chapter, we mainly discuss the synthetic conditions and preparation methods of DNA nano-flowers and the stability of DNA nano-flowers. The DNA nanorods are obtained by liquid crystallization with high local concentration of DNA. The synthesis of DNA nanorods requires DNA polymerase. Template and primer DNA strands are involved. The synthesis of DNA nanoflower is affected by many conditions, such as the type and concentration of DNA polymerase, the sequence of DNA template chain, the reaction time and so on. In this chapter, the effects of these conditions on the synthesis of DNA nano-flower were discussed one by one. In addition, the stability of DNA nanoparticles at different temperatures, enzymes, complex systems and drugs were discussed. Chapter 3 mainly introduces the application of DNA nanoflores in targeting cancer cells. In this chapter, we investigate the effect of DNA nanoparticles on two groups of drug resistant and non-resistant cancer cell lines. The main contents include the binding ability of DNA flower granules to target cancer cells, the penetration ability of target cancer cells membrane, the growth inhibition ability of target cancer cells, and so on. The ability of DNA flower granule to deliver cancer was evaluated from many aspects, and its advantages and disadvantages compared with traditional nano-DNA drug carrier were compared. Chapter 4 mainly introduces the application of DNA flower granules in cell polychromatic imaging. In this chapter, polychromatic DNA nanorods with resonance transfer of fluorescence energy were synthesized by doping a variety of dye molecules. Under the same excitation wavelength, the polychromatic DNA nano-flower can emit different polychromatic fluorescence according to the ratio of different doped fluorescent dyes. The polychromatic DNA nanoparticles can be used to monitor multiple targets in biological system in real time, which is of great significance in clinical application.
【学位授予单位】：湖南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R730.5;TB383.1

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