基于金纳米簇多功能生物纳米探针的设计、合成及其应用研究

发布时间：2018-04-05 07:07

本文选题：金纳米簇　切入点：有机无机复合纳米材料　出处：《太原理工大学》2017年硕士论文

【摘要】：无机纳米材料,尤其是金纳米材料,由于具有独特的表面等离子体效应、光电性质以及生物相容性等优势,在生物传感器、靶向给药、生物组织和细胞成像及动力学治疗等领域有着极其广阔的应用前景。金纳米材料通过表面工程化修饰可有效改善其发光性能,并赋予其表面拉曼增强成像以及载药、治疗等功能,实现生物纳米探针诊疗一体化,从而引起了科研人员广泛而深入的关注。在本论文中,我们利用不同氨基酸修饰金纳米簇,再与其他有机功能分子通过化学键作用复合与组装,实现了有机无机复合型多功能生物纳米探针的制备,并成功应用于生物成像中。在第二章中,我们利用谷胱甘肽(GSH)还原高氯金酸合成金纳米簇,接着与β-环糊精(β-CD)通过酯化反应得到化学键合的Au-GS@β-CD复合纳米粒子。经实验测试表明,Au-GS@β-CD纳米粒子(NPs)实现了红光发射,且随着浓度的增加,发射强度逐渐增强。细胞毒性实验表明,Au-GS@β-CD NPs毒性低,生物相容性好。激光扫描共聚焦显微镜成像结果表明,Au-GS@β-CD NPs对胃癌细胞(MGC-803)具有选择透过性,可进行特异性荧光标记。温度响应实验结果表明,随着温度的升高,Au-GS和Au-GS@β-CD NPs荧光强度逐渐变弱。金属离子检测结果表明,Au-GS和Au-GS@β-CD NPs都对Pb2+、Al3+、Cu2+、Ag+和Fe3+作出了响应。在第三章中,我们设计并合成了一系列磁性荧光纳米粒子Fe3O4@Au,Fe3O4@Au@SiO2,Fe3O4@Au@β-CD;对其结构和性能进行了详细表征,这三种材料都实现了磁共振成像和荧光成像能力的结合,其中Fe3O4@Au@β-CD NPs呈现明显的核壳结构,且水溶性要明显优于Fe3O4@Au和Fe3O4@Au@SiO2 NPs,同时最大荧光发射峰红移,实现红色荧光发射。随着浓度的增加,三种磁性纳米材料荧光发射强度均明显增强。细胞毒性实验表明,Fe3O4@Au,Fe3O4@Au@SiO2和Fe3O4@Au@β-CD NPs均具有较低的生物毒性,而Fe3O4@Au@β-CD NPs由于其高水溶性表现出良好的生物相容性。激光扫描共聚焦显微镜成像结果表明Fe3O4@Au@β-CD NPs对胃癌细胞(MGC-803)具有良好的选择透过性,因此可以进行特异性标记。在第四章中,我们将铂卟啉(Pt-TCPP)与金纳米簇(Au-L-cys)通过酯化反应进行化学键合生成Au-L-cys@Pt-TCPP有机无机复合纳米粒子,该纳米粒子兼具金属卟啉和金纳米簇的性能,其最大发射峰到达红光区域。细胞毒性实验表明,Au-L-cys@Pt-TCPP NPs具有较低的生物毒性和良好的生物相容性。此外,激光扫描共聚焦显微镜成像结果表明Au-L-cys@Pt-TCPP NPs对胃癌细胞(MGC-803)有较好的选择透过性,可实现特异性红光成像标记。同时对HeLa细胞实现了双波段检测功能:蓝光波段(420-480 nm)和红光波段(620-680 nm)。综上所述,本论文基于对金纳米簇和磁性荧光纳米粒子的表面工程化修饰,实现了多功能高水溶性生物纳米探针的合成,为癌细胞诊疗一体化试剂的研发提供了极具应用前景的候选材料。
[Abstract]:Inorganic nanomaterials, especially gold nanomaterials, because of their unique surface plasma effect, optoelectronic properties and biocompatibility, are used in biosensor, targeted drug delivery, etc.Biological tissue and cell imaging and kinetic therapy have broad application prospects.Gold nanomaterials can effectively improve their luminescence performance by surface engineering modification, and endow them with the functions of surface Raman enhanced imaging, drug loading and therapy, so as to realize the integration of biological nano-probe diagnosis and treatment.Thus caused the scientific research personnel widespread and the thorough concern.In this thesis, we used different amino acids to modify gold nanoclusters, and then we combined and assembled with other organic functional molecules by chemical bond to achieve the preparation of organic-inorganic multifunctional biological nanoprobes.And successfully applied in biological imaging.In chapter 2, we use glutathione glutathione (GSH) to reduce gold nanoclusters with high chloro gold acid, and then we react with 尾 -cyclodextrin (尾 -CD) to obtain chemically bonded Au-GS@ 尾 -CD composite nanoparticles.The experimental results show that the red light emission is realized by Au-GS@ 尾 -CD nanoparticles (NPs), and the emission intensity increases with the increase of concentration.Cytotoxicity test showed that Au-GS @ 尾 -CD NPs had low toxicity and good biocompatibility.The results of laser scanning confocal microscopy showed that Au-GS @ 尾 -CD NPs had selective permeability to gastric cancer cell line MGC-803 and could be labeled with specific fluorescence.The results of temperature response experiments show that the fluorescence intensity of Au-GS and Au-GS@ 尾 -CD NPs weakens with the increase of temperature.The results of metal ion detection show that both Au-GS and Au-GS @ 尾 -CD NPs are responsive to Pb2 Al3 + Cu2 + Ag and Fe3.In Chapter 3, we have designed and synthesized a series of magnetic fluorescent nanoparticles Fe _ 3O _ 4O _ 4O _ (Fe3O _ 4) Au@ 尾 -CD.The structure and properties of these materials have been characterized in detail. The three materials have realized the combination of magnetic resonance imaging (MRI) and fluorescence imaging.Fe3O4 @ 尾 -CD NPs has obvious core-shell structure, and its water solubility is obviously superior to that of Fe3O4@Au and Fe3O4@Au@SiO2 NPs. Meanwhile, the maximum fluorescence emission peak shifts red to realize red fluorescence emission.With the increase of the concentration, the fluorescence emission intensity of the three kinds of magnetic nanomaterials increased obviously.The cytotoxicity tests showed that Fe3O4R, Fe3O4R, Fe3O4R, SiO2 and Fe3O4R @ 尾 -CD NPs had lower biotoxicity, while Fe3O4R Au@ 尾 -CD NPs showed good biocompatibility due to its high water solubility.The results of laser scanning confocal microscopy showed that Fe3O4R Au@ 尾 -CD NPs had a good selective permeability to gastric cancer cell line MGC-803, so it could be labeled specifically.In chapter 4, we chemically bond platinum porphyrin (Pt-TCPP) with gold nanoclusters Au-L-cyss to form Au-L-cys@Pt-TCPP organic-inorganic composite nanoparticles, which have the properties of both metalloporphyrin and gold nanoclusters.The maximum emission peak reaches the red region.Cytotoxicity test showed that Au-L-cysr Pt-TCPP NPs had low biotoxicity and good biocompatibility.In addition, the results of laser scanning confocal microscopy showed that Au-L-cys@Pt-TCPP NPs had a better selective transmittance to gastric cancer cell line MGC-803, and could be used as a specific red light imaging marker.At the same time, the HeLa cells were detected in two bands: blue band (420-480 nm) and red light band (620-680 nm).In conclusion, based on the surface engineering modification of gold nanoclusters and magnetic fluorescent nanoparticles, the synthesis of multifunctional and highly water-soluble biological nanoprobes has been achieved.It provides a promising candidate material for the research and development of cancer cell diagnosis and treatment integration reagent.
【学位授予单位】：太原理工大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1;O657.3

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