基于秀丽隐杆线虫的荧光碲化镉量子点和硅纳米颗粒的生物安全性研究

发布时间：2018-06-28 22:37

本文选题：量子点 + 线虫　；参考：《苏州大学》2016年硕士论文

【摘要】：近年来,随着纳米材料的迅速发展,半导体荧光量子点和荧光硅纳米颗粒作为具有代表性的荧光纳米材料,由于其优良的光学性质,在生物学及生物医学领域有着广泛的应用。随着对荧光纳米材料生物应用的日益深入,其生物安全性得到了科研工作者们的广泛关注。秀丽隐杆线虫由于具有优异的特性和研究的优势(例如,可以实现同时在整体水平和亚细胞水平上进行研究,且遗传进化保守的特点也使得与线虫相关的研究具有重大的价值),因而被科研工作者们作为模式动物来研究纳米材料的生物安全性。因此,在本文中,我们利用线虫作为动物模型系统地研究了碲化镉量子点和荧光硅纳米颗粒的生物安全性。首先,本文从整体水平和亚细胞水平对三种不同尺寸的碲化镉量子点在线虫体内的行为学以及毒理学进行了系统的研究。实验数据表明碲化镉量子点在线虫体内的分布和毒性有着一定的尺寸依赖性。量子点短时间的处理会抑制线虫的生长发育,对线虫的寿命没有明显的影响,表明量子点短时间的处理对线虫产生的影响是急性的,不会造成永久性的损伤。但是,量子点长时间的处理会抑制线虫的生长发育并缩短其寿命,造成的影响是难以恢复的。因此,与体外培养的细胞不同,线虫可以承受量子点短时间处理所带来的影响。若量子点长时间滞留在线虫体内,则对线虫造成的影响是不可恢复的。通过对亚细胞结构的检测与分析,证明碲化镉量子点破坏了线虫体内细胞的胞吞过程以及营养贮存过程,这可能是量子点造成线虫生长抑制和寿命缩短的根本原因。本文揭示了碲化镉量子点会破坏生物体内细胞过程的稳态,其在组织和器官中长久的累积会造成无法恢复的损伤。上述研究结果为了解量子点的生物安全性提供了一定的参考。其次,本文利用哺乳动物细胞和线虫研究了硅纳米颗粒对自噬的调控情况。具体而言,通过将硅纳米颗粒对细胞和线虫进行处理,结果表明硅纳米颗粒没有引起细胞与线虫体内自噬小体的形成。经过硅纳米颗粒处理的细胞与线虫,体内自噬相关基因的转录水平没有发生上调,且自噬相关蛋白的表达量也没有升高。而且在不同的处理时间条件下,硅纳米颗粒均没有引起细胞中自噬小体的形成。通过实时地检测线虫体内自噬小体数目的变化,也进一步表明硅纳米颗粒没有引起线虫体内自噬小体的形成。综上所述,上述研究结果初步表明了硅纳米颗粒在适宜成像的浓度下没有引起细胞与线虫产生自噬,这为了解硅纳米颗粒与自噬的关系提供了一定的信息。
[Abstract]:In recent years, with the rapid development of nanomaterials, semiconductor fluorescent quantum dots and fluorescent silicon nanoparticles, as representative fluorescent nanomaterials, have been widely used in biological and biomedical fields because of their excellent optical properties. With the increasing application of fluorescent nanomaterials, the biosafety of fluorescent nanomaterials has been paid more and more attention by researchers. Because of its excellent properties and research advantages (for example, it can be achieved at both the overall and subcellular levels). The conservation of genetic evolution also makes the research related to nematodes of great value. Therefore, researchers have been used as model animals to study the biological safety of nanomaterials. Therefore, in this paper, the biological safety of cadmium telluride quantum dots and fluorescent silicon nanoparticles were systematically studied using nematodes as animal models. Firstly, the behavior and toxicology of three different sizes of cadmium telluride quantum dots in vivo were systematically studied at the global and subcellular levels. Experimental data show that the distribution and toxicity of cadmium telluride quantum dots in vivo are size dependent. The growth and development of nematodes were inhibited by the treatment of quantum dots for a short time, and the longevity of nematodes was not affected obviously, which indicated that the effects of the treatment of quantum dots on nematodes were acute and would not cause permanent damage. However, the treatment of quantum dots for a long time will inhibit the growth and development of nematode and shorten its life span, and the effect is difficult to recover. As a result, nematodes can withstand the effects of short quantum dot treatments, unlike cells cultured in vitro. If the QDs stay in the nematodes for a long time, the effect on the nematodes is irreversible. Through the detection and analysis of the subcellular structure, it is proved that the cadmium telluride quantum dots destroy the process of endocytosis and nutrient storage of nematode cells, which may be the root cause of the inhibition of growth and the shortening of life span of nematodes. This paper reveals that cadmium telluride quantum dots can destroy the steady-state of cell process in organism and the accumulation of cadmium telluride quantum dots in tissues and organs can cause irreparable damage. These results provide a reference for understanding the biological safety of quantum dots. Secondly, the regulation of silicon nanoparticles on autophagy was studied by mammalian cells and nematodes. In particular, by treating cells and nematodes with silicon nanoparticles, the results showed that the formation of autophagy bodies in cells and nematodes was not induced by silicon nanoparticles. The transcription level of autophagy related gene was not up-regulated and the expression of autophagy related protein was not increased in the cells and nematodes treated with silicon nanoparticles. In addition, no autophagy formation was induced by silicon nanoparticles at different treatment time. Through real-time detection of the number of autophagy bodies in nematodes, it is further indicated that the formation of autophagy bodies in nematodes is not caused by silicon nanoparticles. To sum up, the above results show that silicon nanoparticles do not induce autophagy between cells and nematodes at suitable imaging concentration, which provides some information for understanding the relationship between silicon nanoparticles and autophagy.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R114;TB383.1

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