【作者】 杨畅；

【导师】 项光亚； 陈伟；

【作者基本信息】 华中科技大学 ， 药理学， 2013， 博士

【摘要】 20世纪80年代初,科学家们发现,当某些材料的尺寸处于介观状态时,其宏观性质会发生巨大的改变,而且当材料的尺寸降至纳米范围时,许多新奇的性能出现了,并且这些性能是不能被传统的理论所预知的。因此,对纳米材料的研究极具挑战性。纳米尺度的贵金属材料(如金、银等),因其突出的催化性质、电性质、磁性质和光学性质,已经成为纳米科技领域中最富有活力的研究热点之一。本论文主要研究金纳米团簇的荧光性质,以及利用银纳米颗粒的局部表面等离子体共振性质来增强硫化铜纳米颗粒在近红外区域的吸收以提高硫化铜纳米颗粒的光热转换效率,使其能更有效地用于光热疗法治疗肿瘤。(1)采用谷光甘肽作为稳定剂和温和的还原剂,以不同的比例与三氯化金混合,制备得到红色荧光和近红外荧光的金纳米团簇。运用紫外可见吸收光谱、荧光光谱、HRTEM、FTIR、XPS等技术对金纳米团簇进行表征,发现荧光金纳米团簇粒径很小,约2nm,不具有表面等离子体共振性质,但团簇内含有1价金,因而可以产生荧光。对其发光机理进行初步研究发现,金原子与巯基配体之间杂合轨道的分裂能级是其产生红色荧光和近红外荧光的基础,分别为受激电子从单重态或三重态返回到基态时所发射。同时,我们还对其X射线荧光以及其用于细胞显像进行了初步研究。实验结果显示,荧光金纳米团簇在固体基质中具有X射线荧光性质,在放射性探测和生物靶向传递等方面都可能有进一步的应用。另一方面,细胞可以摄取荧光金纳米团簇,用于细胞显像。(2)贵金属纳米颗粒金、银、铜等具有表面等离子体共振性质,在紫外可见光照射下可产生鲜亮的颜色,并且产生一定的热。医学上利用贵金属纳米颗粒的这种性质治疗肿瘤,称为光热疗法。目前常用的光热疗法治疗制剂有金纳米颗粒、碳纳米棒以及硫化铜纳米颗粒。其中硫化铜以其制备简单、成本低、易于修饰,受到了很多科学家的关注。但是其光热转换效率不如金纳米颗粒,于是我们试图利用比金廉价的银纳米颗粒来增强硫化铜纳米颗粒在近红外区域的吸收。因为金和银纳米颗粒具有表面等离子体共振性质,所以可以与Cu2+d-d轨道耦合,增强硫化铜纳米颗粒在近红外区域的光吸收,从而增加其光热转换效率。实验结果证明,Ag/CuS纳米复合物的确比CuS纳米颗粒有更强的近红外吸收,增强了将近4倍,其光热转换效率也得到了进一步加强。利用Ag/CuS纳米复合物的荧光性质,我们研究了其在前列腺肿瘤细胞内的时程吸收。在孵育4个小时后,细胞吸收达到了饱和。当Ag/CuS纳米复合物用于光热疗法治疗肿瘤时,980nm近红外激光作为辐射光源。在0.6W/cm2的照射强度下照射5分钟,就能有效的杀伤肿瘤细胞,达到了美国980nm激光安全辐射范围(0.726W/cm2)的标准。因此,我们认为Ag/CuS纳米复合物是一种极具发展前景的光热疗法治疗制剂。更多还原

【Abstract】 Since1980s, the scientists have realized that the properties of the materials will be greatly changed if the sizes are reduced in the range of mesoscopic scale. Many novel properties are beyond traditional theories when the materials are nanosized. Thus, they are of challenges. The noble metal nanomaterials have become one of the most active branches in nanotechnological area because of their distinct catalytic, electronic, magnetic, and luminescent properties. In this dissertation, we focus on the luminescent properties of gold nanoparticles and the photo thermal therapy on cancer using Ag/CuS nanocomposites.(1) Glutathione as a stabilizer and a soft reducer, were mixed with AuCI2as a1:1or5:4ratio to obtain red luminescent or near-infrared luminescent gold nanoclusters. UV-vis absorption, photoluminescence spectra, high resolution transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and so on, were used to characterize the gold nanoclusters. On one hand, results show that the size of gold nanoclusters is very small about2nm without the representative absorption of surface plasmon resonance around520nm. XPS analysis reveal the nature of luminescent gold nanoparticles with mixed valence states generated from dissociation of polymeric Au(I) thiolates. On the other hand, the potential application of gold nanoclusters in the X-ray luminescence and cell imaging were also explored.(2) The noble metal nanoparticles such as gold, silver and copper have the surface plasmon resonance to result In the bright colors. And heat will also be produced to kill cancer cells, which is called photothermal therapy. So far, the common photothermal agents are gold nanoparticles, carbon nanotube and copper sulfide nanoparticles. Cooper sulfide nanoparticles have attracted a lot of attentions from scientists due to simple preparation, low cost and easy modification. However, their photothermal transfer efficiency is not as good as gold nanoparticles. Thus, we try to use the local surface plasmon resonance (LSPR) of silver nanoparticles to enhance the absorption of copper sulfide nanoparticles in the near-infrared region. The results show that the absorbance of CuS nanoparticles in Ag/CuS nanocomposites is enhanced about4times by Ag nanoparticle surface plasmon coupling. The corresponding photothermal transfer efficiency is also enhanced by the temperature measurement in the solution. Using the luminescent properties of Ag/CuS nanocomposites, the time course cell uptake is also carried out. Ag/CuS nanocomposites can get into PC-3cells and are mainly located in their cytoplasm. After4hours incubation, the cell uptake is saturated and the luminescence reaches the brightest. Finally, a power per area of0.6W/cm2with a980nm laser is sufficient to kill cancer cells for Ag/CuS nanocomposite-PTT activation in vitro observations, which is in the range of the conservative limit of980nm laser intensity (0.726W/cm2). In summary, Ag/CuS nanocomposites are a new and promising modality for cancer treatment.更多还原