基于空心金纳米球的多功能纳米颗粒的制备及其在生物医学中的应用

发布时间：2018-01-18 05:20

本文关键词：基于空心金纳米球的多功能纳米颗粒的制备及其在生物医学中的应用　出处：《华中科技大学》2015年硕士论文　论文类型：学位论文

【摘要】：将成像和治疗功能结合在一个纳米结构中的诊疗试剂能够实现肿瘤的早期诊断与治疗,为癌症的早发现、早治疗提供科学保障。在众多的诊疗试剂中,多功能磁-金复合纳米结构因结合了磁性纳米材料优良的磁学性能和金纳米材料良好的光学性能而受到了广泛关注。研究者对多功能磁-金复合纳米结构已经进行了广泛的研究,但是这些研究大部分集中于磁性纳米颗粒与金纳米棒或纳米壳的结合,而很少有关于空心金纳米球(HGNs)与磁性纳米颗粒相结合应用于肿瘤多模成像和治疗的报道。相较于其它形貌的金纳米结构,HGNs拥有尺寸小(~50 nm)、球形、强烈且可调至近红外光区的光学吸收特性等众多优势,特别是它的空腔结构,使它成为装载功能试剂(如抗肿瘤药物)的理想载体,可以实现光疗与化疗的结合。基于此,我们设计了一种新型的多功能磁-金复合纳米结构HGNs@Fe3O4-FA,该结构以HGNs为核心,用共价偶联的方式将Fe3O4纳米颗粒和肿瘤靶向分子叶酸(FA)修饰在HGNs的表面。该结构可同时实现肿瘤细胞的MRI/光声双模成像和光热治疗功能。此外,我们还结合荧光成像的灵敏性,设计了一种具备肿瘤光声/荧光双模成像功能的多功能复合纳米结构,并将抗肿瘤药物阿霉素(DOX)装载于此结构中,以实现肿瘤化疗与光热治疗的结合。具体研究内容包括:(1)多功能磁性空心金纳米球HGNs@Fe3O4-FA的合成与表征。首先,用钴模板替代法合成水溶性HGNs,然后用多元醇法合成超顺磁性Fe3O4纳米颗粒并对其进行表面巯基化修饰,并使其通过Au-S键与HGNs共价偶联。最后,用半胱胺盐酸盐作为连接分子、DCC/NHS作为偶联剂,在HGNs表面修饰肿瘤靶向分子叶酸(FA)。研究并证实了该探针有较好的MRI/光声双模成像功能和良好的光热转换效果。(2)多功能荧光载药纳米颗粒HGNs@RhB@BSA-DOX的合成与表征。首先,用偶联剂EDC/Sulfo-NHS将荧光染料罗丹明B(RhB)共价偶联在牛血清白蛋白(BSA)上。然后,通过BSA上巯基与Au原子的相互作用,将BSA和HGNs共价偶联在一起。最后,通过静电和疏水相互作用将抗肿瘤药物DOX装载到纳米颗粒上。并用紫外光谱仪、荧光光谱仪、粒度仪等仪器对该纳米颗粒进行了表征。(3)对HGNs@Fe3O4-FA纳米颗粒进行毒性评估并将其应用于体外肿瘤细胞的光声/MRI双模成像及肿瘤光热治疗的研究。MTT实验结果显示,在探针浓度高达200μg/mL时,细胞仍有80%以上的存活率,表明该纳米颗粒毒性很小。另外,研究并证实了该纳米颗粒具有良好的体外细胞MRI/光声双模成像效果和优良的光热治疗效果。以上结果显示了该纳米颗粒作为诊疗试剂的巨大应用潜力。
[Abstract]:The combination of imaging and treatment functions in a nanostructure can achieve the early diagnosis and treatment of cancer, and provide a scientific guarantee for the early detection and treatment of cancer. The multifunctional magnetic-gold nanostructures have attracted much attention for their combination of the excellent magnetic properties of the magnetic nanomaterials and the good optical properties of the gold nanomaterials. Well, extensive research. But most of these studies focus on the combination of magnetic nanoparticles with gold nanorods or nanoshells. However, there are few reports on the application of hollow gold nanospheres (HGNs) combined with magnetic nanoparticles in tumor multimode imaging and treatment, compared with other gold nanostructures. HGNs has many advantages, such as small size of 50nm, spherical, strong and adjustable optical absorption characteristics to near infrared region, especially its cavity structure. Making it an ideal carrier for loading functional reagents (such as antitumor drugs) can combine phototherapy with chemotherapy. We have designed a novel multifunctional magneto-gold nanostructure, HGNs @ Fe3O4-FA.HGNs @ Fe3O4-FA.The structure is based on HGNs. Covalent Coupling of Fe3O4 nanoparticles and tumor targeting Molecular folate. Modified on the surface of HGNs. This structure can achieve both MRI / photoacoustic dual-mode imaging and photothermal therapy of tumor cells. Considering the sensitivity of fluorescence imaging, we designed a multifunctional composite nanostructure with tumor photoacoustic / fluorescent dual-mode imaging function, and loaded the anti-tumor drug doxorubicin (DOX) into the structure. In order to achieve the combination of tumor chemotherapy and photothermal therapy. The specific research contents include the synthesis and characterization of multifunctional magnetic hollow gold nanospheres (HGNs@Fe3O4-FA). Water soluble HGNs were synthesized by cobalt template substitution method, and then superparamagnetic Fe3O4 nanoparticles were synthesized by polyol method and modified by surface sulfhydrylation. Finally, cysteamine hydrochloride was used as the coupling molecule DCC-NHS as the coupling agent. Modification of tumor targeting molecule folate on the surface of HGNs has been studied and confirmed that the probe has better function of MRI / photoacoustic dual-mode imaging and good photothermal conversion effect. Synthesis and characterization of multifunctional fluorescent drug-loaded nanoparticles HGNs@RhB@BSA-DOX. The fluorescent dye Rhodamine (RhB) was covalently coupled to bovine serum albumin (BSA) by coupling agent EDC/Sulfo-NHS. BSA and HGNs are covalently coupled by the interaction of sulfhydryl group with au atom on BSA. Finally. The antitumor drug DOX was loaded onto the nanoparticles by electrostatic and hydrophobic interaction. The nanoparticles were characterized by granulometer and other instruments. The toxicity of HGNs@Fe3O4-FA nanoparticles was evaluated and applied to the study of photoacoustic / MRI dual-mode imaging and photothermal therapy of tumor cells in vitro. When the probe concentration was as high as 200 渭 g / mL, the cell still had a survival rate of more than 80%, indicating that the nanoparticles had little toxicity. The results show that the nanoparticles have a good in vitro MRI / photoacoustic dual-mode imaging and excellent photothermal therapy. The results show that the nanoparticles have great application potential as diagnostic and therapeutic reagents.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：TB383.1;O614.123

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