纳米颗粒与细胞膜外基质相互作用的影响因素研究

发布时间：2018-12-15 21:06

【摘要】：随着纳米技术的发展，纳米颗粒的可控合成和修饰使其越来越受到研究者的关注而被广泛应用于生物医学和生物技术领域。将纳米材料运用到生物环境中需要考虑的首要问题是纳米颗粒的细胞反应，因此纳米颗粒与细胞的相互作用研究显得尤为重要。细胞膜外基质是存在于真核细胞外的一层凝胶状透明物质，不仅在细胞的增值和分化、粘附和迁移等方面发挥着非常重要的作用，而且研究者发现膜外基质还可以捕获聚集纳米颗粒、降低其运动速度并促进其细胞内吞效率。因此，，在纳米颗粒与细胞的相互作用研究中，细胞膜外基质成为一个必须要考虑的重要因素。影响纳米颗粒与细胞的因素有很多，如纳米颗粒的尺寸和形貌、纳米颗粒的亲疏水性质、纳米颗粒的表面化学等等。这些因素影响了纳米颗粒与细胞的作用方式和作用机理，从而产生了不同的作用结果，因此我们需要对这些因素的影响进行探究。在本文中，我们以金纳米颗粒和聚苯乙烯纳米颗粒为探针，研究了一系列因素对纳米颗粒与细胞膜外基质相互作用的影响。 1、用具有较厚膜外基质的骨肉瘤MG-63细胞作为厚膜外基质细胞模型，用透明质酸酶处理的MG-63细胞作为薄膜外基质细胞模型。研究了不同尺寸的金纳米颗粒和聚苯乙烯纳米颗粒与厚、薄膜外基质细胞的相互作用。研究发现膜外基质对尺寸大于50nm的颗粒具有显著的捕获作用，而对尺寸在20nm左右的颗粒没有明显促进捕获作用，而且这种尺寸效应不依赖于纳米颗粒的材料。 2、以具有较薄膜外基质的乳腺癌HeLa细胞作为模型，以抗坏血酸处理过的HeLa细胞作为具有较厚膜外基质的细胞，用透明质酸酶处理的HeLa细胞作为具有较薄膜外基质的细胞，研究了70-120nm金纳米颗粒与具有不同厚度膜外基质细胞的相互作用，发现在HeLa细胞系中，膜外基质对大颗粒同样具有显著的捕获作用，说明膜外基质对大颗粒的捕获作用是具有普遍性的。 3、研究了具有不同表面电荷的纳米颗粒与细胞膜外基质的相互作用，发现膜外基质对不同表面电荷的纳米颗粒均具有显著捕获作用。最后通过研究纳米颗粒与抑制剂处理过的细胞的相互作用，发现膜外基质对纳米颗粒的捕获大大降低，说明细胞膜外基质对纳米颗粒的捕获作用不是一个独立的生物过程，而是受体介导内吞的一部分。
[Abstract]:With the development of nanotechnology, the controllable synthesis and modification of nanoparticles have attracted more and more attention of researchers and have been widely used in biomedicine and biotechnology fields. The first problem to be considered in the application of nanomaterials to biological environment is the cellular reaction of nanoparticles, so the study of the interaction between nanoparticles and cells is particularly important. Extracellular matrix is a gelatinous transparent substance that exists outside eukaryotic cells. It not only plays an important role in cell proliferation and differentiation, adhesion and migration. Moreover, the researchers found that the extracellular matrix can also capture and aggregate nanoparticles, slow down their motion and promote their endocytosis efficiency. Therefore, extracellular matrix has become an important factor to be considered in the study of the interaction between nanoparticles and cells. There are many factors that affect the size and morphology of nanoparticles, hydrophobic properties of nanoparticles, surface chemistry of nanoparticles and so on. These factors influence the way and mechanism of action between nanoparticles and cells, which result in different effects. Therefore, we need to explore the effects of these factors. In this paper, we used gold nanoparticles and polystyrene nanoparticles as probes to study the effects of a series of factors on the interaction between nanoparticles and extracellular matrix. 1Osteosarcoma MG-63 cells with thicker extracellular matrix and MG-63 cells treated with hyaluronidase were used as the model of thick extracellular matrix cells. The interaction of gold nanoparticles and polystyrene nanoparticles with thick, thin film extracellular matrix was studied. It is found that the extracellular matrix has a significant trapping effect on the particles larger than 50nm, but not on the particles about the size of 20nm, and this size effect is independent of the nanoparticles. 2. Breast cancer HeLa cells with more extracellular matrix were used as model, HeLa cells treated with ascorbic acid as cells with thicker extracellular matrix and HeLa cells treated with hyaluronidase as cells with more membrane extracellular matrix. The interaction between gold nanoparticles of 70-120nm and extracellular matrix cells with different thickness was studied. It was found that in HeLa cell line, extracellular matrix also had significant trapping effect on large particles. It shows that the capture of large particles by the extracellular matrix is universal. 3. The interaction between the nanoparticles with different surface charges and the extracellular matrix was studied. It was found that the extracellular matrix had a remarkable trapping effect on the nanoparticles with different surface charges. Finally, by studying the interaction between nanoparticles and the cells treated with inhibitors, it is found that the capture of nanoparticles by extracellular matrix is greatly reduced, which indicates that the capture of nanoparticles by extracellular matrix is not an independent biological process. It is part of the receptor that mediates endocytosis.
【学位授予单位】：湖南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R318.08;TB383.1

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