表面性质连续变化的金纳米系列的制备及其诱导细胞自噬的初步研究

发布时间：2018-04-26 19:17

本文选题：金纳米系列 + 功能化修饰　；参考：《山东大学》2015年硕士论文

【摘要】：自上世纪六十年代末诺贝尔奖得主Richard Feynman首次提出纳米科学技术这一概念,纳米科技便飞速发展并渗透入能源、建筑、生物医药、环保、工业、生活等各个领域。随着纳米科技的广泛应用,纳米材料正以各种不同的方式和途径进入我们所处的生态环境,并对生态环境和人类健康带来潜在的危害。研究表明,纳米颗粒的生产、运输及使用的整个过程都会造成其在环境中的释放和扩散。纳米颗粒可以经呼吸暴露、皮肤暴露、口服暴露和注射暴露等途径进入人体,并经淋巴循环、血液循环进入机体各种脏器,引起机体应激反应。随着对纳米材料生态效应研究的深入,我们亟需系统研究纳米材料的性质如何影响其生物效应,从而为科学、安全的使用纳米材料提供理论支持。目前的研究表明,纳米材料的成分、粒径、形貌、表面性质等可影响纳米材料的生物效应。其中纳米—生物界面的主要作用力静电相互作用,疏水相互作用,氢键相互作用,π-π共轭作用,空间位阻等在纳米材料的生物效应方面发挥关键性作用。为了系统阐明纳米材料的表面性质如何影响其生物效应,本课题组选择了广泛应用于诊断、治疗、载药等领域的金纳米材料作为模型,通过对其表面进行功能化修饰,分别设计合成了表面亲疏水性、电荷、氢键、Π键和空间位阻单一性质连续变化的五种金纳米系列用于生物效应研究。本工作为纳米材料表面Π键密度连续变化的金纳米系列的设计、合成、表征及五种金纳米系列对细胞自噬影响的初步研究。本工作第一部分采用酰胺缩合的方法将苯胺(含π键)和环己胺(不含π键)分别与硫辛酸反应,得到N-苯基硫辛酰胺和环己基硫辛酰胺两种小分子配体,使用硼氢化钠还原法将这两种小分子配体按照一定的比例要求通过金硫键连接到金纳米表面对其进行功能化修饰,得到表面Π键密度连续变化的金纳米系列,并利用TEM、DLS、Zeta电位等对金纳米系列进行表征。结果表明我们合成的六种金纳米颗粒均为粒径在5～7nm之间的疏水性球形纳米粒子,其在溶液中基本都以较为稳定的聚集态存在,符合我们的设计要求。本工作的第二部分研究了表面单一性质连续变化的五种金纳米系列对转染了GFP-LC3的人星形胶质瘤细胞系U87的自噬诱发能力,结果表明,亲疏水性连续变化的金纳米系列和表面电荷连续变化的金纳米系列可以引起明显的细胞自噬水平上调,且随着疏水性的增强以及表面电荷密度的增大细胞自噬水平提高,其他三种性质连续变化的金纳米系列诱发细胞自噬的能力较弱,且没有表现出明显的趋势。本研究结果为合理、安全的利用金纳米材料提供了理论基础。
[Abstract]:Since Nobel laureate Richard Feynman first put forward the concept of nanotechnology in the late 1960s, nanotechnology has developed rapidly and penetrated into energy, architecture, biomedicine, environmental protection, industry, life and other fields. With the wide application of nanotechnology, nanomaterials are coming into our ecological environment in various ways and means, and bring potential harm to ecological environment and human health. It is shown that the whole process of production, transportation and use of nanoparticles will result in their release and diffusion in the environment. Nanoparticles can enter the human body through respiratory exposure, skin exposure, oral exposure and injection exposure, and through lymphatic circulation, blood circulation into various organs of the body, causing stress response. With the further study of the ecological effects of nanomaterials, we need to systematically study how the properties of nanomaterials affect their biological effects, so as to provide theoretical support for the scientific and safe use of nanomaterials. Recent studies have shown that the composition, particle size, morphology and surface properties of nanomaterials can affect the biological effects of nanomaterials. Among them, electrostatic interaction, hydrophobic interaction, hydrogen bond interaction, 蟺-蟺 conjugation and steric hindrance play a key role in the biological effects of nanomaterials. In order to elucidate how the surface properties of nanomaterials affect their biological effects, our team selected gold nanomaterials, which are widely used in the fields of diagnosis, treatment, drug loading and so on, as models, and modified their surfaces by functionalization. Five kinds of gold nanocrystals, including hydrophobic surface, charge, hydrogen bond, 蟺 bond and single steric resistance, have been designed and synthesized to study biological effects. This work is the design, synthesis, characterization and preliminary study of the effect of five kinds of gold nanocrystalline series on cell autophagy. In the first part of this work, aniline (containing 蟺 bond) and cyclohexylamine (without 蟺 bond) were reacted with lipoic acid by amide condensation method to obtain two small molecular ligands, N-phenylthioctylamine and cyclohexylthioctylamine, respectively. Using sodium borohydride reduction method, the two small molecular ligands were connected to the gold nanocrystalline surface by au S bond according to a certain proportion, and the au nanocrystalline series with continuous change in bond density were obtained. The gold nanocrystals were characterized by Tem DLSU Zeta potential. The results show that the six kinds of gold nanoparticles are hydrophobic spherical nanoparticles with the particle size between 5~7nm and they all exist in stable aggregates in solution, which meet our design requirements. In the second part of this work, we studied the autophagy inducing ability of five kinds of gold nanometers with continuous changes in the surface of human astroglioma cell line U87 transfected with GFP-LC3. The results showed that, The hydrophobicity of gold nanoseries and the surface charge of gold nanocrystalline series could increase the level of autophagy, and the level of autophagy increased with the increase of hydrophobicity and surface charge density. The ability of the other three series of gold nanoparticles to induce autophagy was weak and showed no obvious trend. The results provide a theoretical basis for the rational and safe use of gold nanomaterials.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TB383.1;O614.123

【共引文献】