荧光纳米粒子的制备及在肿瘤细胞检测中的应用

发布时间：2018-03-23 01:13

本文选题：智能响应　切入点：荧光纳米粒子　出处：《吉林大学》2017年硕士论文　论文类型：学位论文

【摘要】：荧光分子成像技术作为一种新形的细胞成像手段,具有无辐射,成像速度快和灵敏度较高等优点,在生物标记和细胞成像等领域有许多应用。用于对生物体内肿瘤的发生和转移等进行实时、非侵入式、特异性检测,可以从细胞水平上研究肿瘤内发生的生理或者病理学变化,为实践中早期肿瘤的诊断和在手术中的肿瘤成像提供了新技术支持。近些年来,科研工作者已经合成出许多不同类型和功能的纳米荧光探针,包括量子点、金属纳米簇、上转换荧光纳米材料、复合荧光纳米粒子等。在过去的几十年里,许多科研工作者致力于研究刺激响应性聚合物,尤其是带有荧光性质的聚合物。刺激响应性纳米粒子有许多结合位点,可以将一些功能性分子通过化学或物理的方法修饰到纳米粒子表面,并且具有良好的稳定性和生物相容性。聚合物碳点由于具有尺寸均匀,荧光效率高等优点,逐渐成为热点研究课题。在论文的第二章,我们设计制备了聚合物纳米微球S2[Eu-doped PS-co-PNIPAM/FITC],首先采用微乳液聚合在里面包覆油溶性的稀土配合物,合成了核层带有红色荧光聚合物纳米微球S1,将带负电荷的荧光分子FITC修饰到纳米微球表面,最后获得了具有双荧光,并且具有p H响应的双荧光功能聚合物纳米微球S2。聚合物纳米微球S2尺寸均匀,具有良好的水溶性和较低的生物毒性。特别是所合成的聚合物纳米微球S2具有p H响应性,在p H=4-10的生理范围内随着p H升高,内部红色荧光保持稳定,外部荧光分子FITC的荧光逐渐增强。针对正常细胞与肿瘤细胞的p H不同,所制备的纳米微球可以区分检测两种细胞。激光共聚焦细胞成像结果表明这种双荧光聚合物纳米微球S2材料可以用于区分肿瘤细胞和正常细胞。在论文的第三章,我们进一步加深对荧光纳米粒子功能的研究,提高荧光纳米探针的靶向性,我们设计构筑了具有肿瘤靶向性的聚合物碳点类型荧光纳米材料,采用对肿瘤细胞具有靶向作用的叶酸分子为原料,通过水热方法合成了具有荧光性质的聚合物碳点。我们所制备的聚合物碳点为纳米尺寸,具有蓝色荧光,且荧光量子效率较高,利用分子内具有能量共振转移的机理,使聚合物碳点的荧光性质得到增强。特别是聚合物碳点利用表面的叶酸可以特异性结合肿瘤细胞,实现其短时间快速进入肿瘤细胞而几乎不进入正常细胞的特点,达到主动靶向肿瘤的目的,实现区分检测肿瘤细胞和正常细胞,以及进行生物荧光成像的功能。
[Abstract]:Fluorescence molecular imaging technology as a new means of cell imaging, has no radiation, fast imaging speed and sensitivity is relatively high, there are many applications in biological labeling and cell imaging. For in vivo tumorigenesis and metastasis in real-time, non invasion, tumor specific detection, can be studied in the physiological or pathological changes in the cell level, provides a new technical support for the early diagnosis of tumors in practice and in the surgery of tumor imaging. In recent years, researchers have already synthesized nano fluorescent probes of many different types and functions, including quantum dots, metal nanoclusters, upconversion nano composite material, fluorescent nanoparticles. In the past few decades, many researchers devoted to the study of stimuli responsive polymer, especially polymer with fluorescence properties. Sound stimulation Of the nanoparticles have many binding sites, can be some functional molecules by chemical or physical methods to modify the surface of nanoparticles, and has good compatibility and biological stability. Because of the uniform size of polymer carbon, higher fluorescence efficiency has gradually become a hot research topic. In the second chapter, we design the polymer S2[Eu-doped PS-co-PNIPAM/FITC] nanoparticles were prepared firstly by microemulsion polymerization inside coated oil soluble rare earth complexes of the synthesized nuclear layer with red fluorescent polymer nanoparticles S1, FITC fluorescent molecule with negative charge to the surface modification of nanoparticles, finally obtained with dual fluorescence, and has a p double H response fluorescent functional polymeric nanoparticles of S2. polymer nanospheres with uniform size S2, has good water solubility and low toxicity especially. The synthesis of polymer nanoparticles with S2 P H response, P H=4-10 in the physiological range with P H increased internal red fluorescence stable fluorescent molecule FITC external fluorescence gradually increased. In normal cells and tumor cells of P H, the nanoparticles can distinguish the two kinds of cells were detected by laser. Confocal imaging results show that the cell double fluorescent polymer nanoparticles of S2 materials can be used to distinguish between tumor cells and normal cells. In the third chapter, we further study the function of fluorescent nanoparticles, enhanced fluorescence nano probe targeting, we designed and built a tumor type fluorescent nano materials to the polymer carbon the use of targeted molecular folic acid as raw material to tumor cells, the fluorescence properties of polymer carbon is synthesized by hydrothermal method. We prepared For polymer carbon nano size, with blue fluorescence, and the fluorescence quantum efficiency is high, the use of molecular mechanism of resonance energy transfer, the fluorescence properties of polymer carbon is enhanced. Especially using polymer carbon surface folic acid could bind to tumor cells, realize the characteristics of the short time quickly into tumor cells and almost do not enter the normal cell, achieve active targeting to tumor, realize detection of tumor cells and normal cells, and the function of biological fluorescence imaging.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R730.4;TB383.1

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