荧光磁性纳米材料的制备及其在磁共振方面的应用
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摘要
近十几年来,纳米科技得到了迅猛发展,并且广泛渗透于各个学科领域,形成了一系列既相对独立又互相联系的分支学科,其中由纳米科学、生物学和医学交叉结合形成的纳米生物医学,是最引人注目、最有生命力的发展方向之一。生物医用功能纳米材料的制备与应用是其主要研究内容之一。其中,荧光二氧化硅由于具有优越的荧光纳米效应,已经被应用于荧光标记探针、荧光传感器的制备等研究中。磁性纳米材料由于具有粒径小和强的可操纵性而被成功地应用于疾病的诊断与治疗以及生物物质的分离等方面,尤其是其作为造影剂在磁共振成像方面具有非常好的应用前景。本文主要研究了荧光二氧化硅和磁性纳米材料的制备,并对磁性纳米材料作为造影剂在磁共振方面的应用进行了初步探讨。
(1)在没有加入任何无机和有机荧光团的情况下,采用一步法合成有荧光的二氧化硅纳米粒子,用透射电子显微镜和扫描电子显微镜表征了粒子的形貌,用红外光谱证明合成了二氧化硅纳米粒子,用荧光分光光度计测定了荧光强度,并且进一步研究了煅烧温度对粒子荧光强度的影响。结果表明:所得二氧化硅纳米粒子为球形,粒径均匀,直径在160nm左右;在二氧化硅的制备过程中添加无荧光基团的有机硅烷,经煅烧可以产生荧光,荧光发射波长在380 nm左右,荧光强度随煅烧温度先增后减,在500℃煅烧后粒子的荧光强度最强。
(2)通过化学共沉淀法合成磁性纳米粒子,在其表面包裹高分子,形成高分子包裹的磁性纳米粒子。再通过化学反应将细胞特异性抗体连接在包裹后的磁性纳米粒子表面。将这样的纳米粒子生物分子复合物用于识别胰腺癌细胞。结果表明,所制得的纳米粒子生物分子复合物能够有效地识别相应的胰腺癌细胞,将胰腺癌细胞切片后在透射电子显微镜下观察,可以清楚的看到纳米粒子生物分子复合物分散在细胞内部,从而为肿瘤在细胞水平上的诊断提供了一种新的技术手段。
(3)基于纳米粒子生物分子复合物在细胞水平上识别胰腺癌细胞的成功,制备了磁性纳米粒子造影剂,并建立了人胰腺癌细胞株BXPC-3裸鼠皮下移植瘤模型用于胰腺癌的磁共振成像研究。结果表明,磁性纳米粒子造影剂能够有效的识别裸鼠体内的胰腺癌肿瘤,提高肿瘤和正常组织在磁共振成像上的对比度,从而为胰腺癌的早期磁共振诊断提供有用的参考。
The rapid progress of nanoscience and nanotechnology in past decade has made itself being widely applied into many other subjects, and caused the formation of a series of independent but close related interdisciplinaries. Bionanomedicine, which is composed by nanoscience, biology, medicine, is one of the most shining and active research field. One major content of it is the preparation and application of functional biomedical materials. The luminescent silica dioxide , which has a superior fluorescence nanometer effect, was widely applied in research and preparation of fluorescence mark probe and fluorescence sensors. Magnetic nanomaterials, which have advantages of the small size and the strong controllability, are applied successfully in disease's diagnosis and treatment as well as biological materials' separation, particularly it has the very good application prospect as the contrast agent in the magnetic resonance image. This article is focused on the preparation of the luminescent silica dioxide and the magnetic nanomaterials, and has carried on the preliminary discussion on magnetic nanomaterials as the contrast agent used in the magnetic resonance imaging..
(1) This article provides a 'one-pot' process for growing luminescent silica dioxide spheres under basic conditions without the subsequent addition of inorganic or organic fluorophores. This article also provides the configuration of silica dioxide spheres by TEM and SEM. It also illustrates fluorescence intension by fluorescence spectrometer, and it also researches the effect of calcinations temperature to fluorescence intensity of silica dioxide spheres. The result indicates that: the silica dioxide nanoparticles is spherical and uniform in size , about 160nm in diameter; In addition of organic silane in processes and calcinations often make the silica dioxide spheres exhibit luminescence, the fluorescence emission wavelength is about 380nm at all times. As the calcinations temperature changes, the fluorescence intensity cuts after increasing first, and the fluorescent intensity maximum appears in the calcinations temperature of 500℃.
(2) The magnetic nanoparticles were synthesized by the chemical coprecipitation. And the magnetic nanoparticles were coated with macromolecules in the microemulsion. The surface of the nanoparticles was conjugated with a cancer-targeting antibody. Then the functional magnetic nanoparticles were used to detect pancreatic tumor cells. The results showed that the functional magnetic nanoparticles may effectively target to pancreas cancer cells, which offered a new tool for original diagnose of pancreas caner in cell lever.
(3) Based on the success of the functional magnetic nanoparticles used in diagnose of pancreas cells in cell lever, we fabricated the biofunctional magnetic nanoparticles contrast agents and established the pancreas cell line BXPC-3 bare mouse hypodermic transplant lump model for magnetic resonance image research. MRI experiments results in vivo indicated the synthesized conjugated nanoparticles can successfully target to the pancreas cancer and enhance contrast of the tumor and the normal tissue in the magnetic resonance image. Therefore, these target-specific magnetic nanoparticles have potential as contrast agents use in MR imaging of pancreas cancer in vivo.
(1)在没有加入任何无机和有机荧光团的情况下,采用一步法合成有荧光的二氧化硅纳米粒子,用透射电子显微镜和扫描电子显微镜表征了粒子的形貌,用红外光谱证明合成了二氧化硅纳米粒子,用荧光分光光度计测定了荧光强度,并且进一步研究了煅烧温度对粒子荧光强度的影响。结果表明:所得二氧化硅纳米粒子为球形,粒径均匀,直径在160nm左右;在二氧化硅的制备过程中添加无荧光基团的有机硅烷,经煅烧可以产生荧光,荧光发射波长在380 nm左右,荧光强度随煅烧温度先增后减,在500℃煅烧后粒子的荧光强度最强。
(2)通过化学共沉淀法合成磁性纳米粒子,在其表面包裹高分子,形成高分子包裹的磁性纳米粒子。再通过化学反应将细胞特异性抗体连接在包裹后的磁性纳米粒子表面。将这样的纳米粒子生物分子复合物用于识别胰腺癌细胞。结果表明,所制得的纳米粒子生物分子复合物能够有效地识别相应的胰腺癌细胞,将胰腺癌细胞切片后在透射电子显微镜下观察,可以清楚的看到纳米粒子生物分子复合物分散在细胞内部,从而为肿瘤在细胞水平上的诊断提供了一种新的技术手段。
(3)基于纳米粒子生物分子复合物在细胞水平上识别胰腺癌细胞的成功,制备了磁性纳米粒子造影剂,并建立了人胰腺癌细胞株BXPC-3裸鼠皮下移植瘤模型用于胰腺癌的磁共振成像研究。结果表明,磁性纳米粒子造影剂能够有效的识别裸鼠体内的胰腺癌肿瘤,提高肿瘤和正常组织在磁共振成像上的对比度,从而为胰腺癌的早期磁共振诊断提供有用的参考。
The rapid progress of nanoscience and nanotechnology in past decade has made itself being widely applied into many other subjects, and caused the formation of a series of independent but close related interdisciplinaries. Bionanomedicine, which is composed by nanoscience, biology, medicine, is one of the most shining and active research field. One major content of it is the preparation and application of functional biomedical materials. The luminescent silica dioxide , which has a superior fluorescence nanometer effect, was widely applied in research and preparation of fluorescence mark probe and fluorescence sensors. Magnetic nanomaterials, which have advantages of the small size and the strong controllability, are applied successfully in disease's diagnosis and treatment as well as biological materials' separation, particularly it has the very good application prospect as the contrast agent in the magnetic resonance image. This article is focused on the preparation of the luminescent silica dioxide and the magnetic nanomaterials, and has carried on the preliminary discussion on magnetic nanomaterials as the contrast agent used in the magnetic resonance imaging..
(1) This article provides a 'one-pot' process for growing luminescent silica dioxide spheres under basic conditions without the subsequent addition of inorganic or organic fluorophores. This article also provides the configuration of silica dioxide spheres by TEM and SEM. It also illustrates fluorescence intension by fluorescence spectrometer, and it also researches the effect of calcinations temperature to fluorescence intensity of silica dioxide spheres. The result indicates that: the silica dioxide nanoparticles is spherical and uniform in size , about 160nm in diameter; In addition of organic silane in processes and calcinations often make the silica dioxide spheres exhibit luminescence, the fluorescence emission wavelength is about 380nm at all times. As the calcinations temperature changes, the fluorescence intensity cuts after increasing first, and the fluorescent intensity maximum appears in the calcinations temperature of 500℃.
(2) The magnetic nanoparticles were synthesized by the chemical coprecipitation. And the magnetic nanoparticles were coated with macromolecules in the microemulsion. The surface of the nanoparticles was conjugated with a cancer-targeting antibody. Then the functional magnetic nanoparticles were used to detect pancreatic tumor cells. The results showed that the functional magnetic nanoparticles may effectively target to pancreas cancer cells, which offered a new tool for original diagnose of pancreas caner in cell lever.
(3) Based on the success of the functional magnetic nanoparticles used in diagnose of pancreas cells in cell lever, we fabricated the biofunctional magnetic nanoparticles contrast agents and established the pancreas cell line BXPC-3 bare mouse hypodermic transplant lump model for magnetic resonance image research. MRI experiments results in vivo indicated the synthesized conjugated nanoparticles can successfully target to the pancreas cancer and enhance contrast of the tumor and the normal tissue in the magnetic resonance image. Therefore, these target-specific magnetic nanoparticles have potential as contrast agents use in MR imaging of pancreas cancer in vivo.
引文
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[2]张阳德,纳米生物分析化学与分子生物学,化学工业出版社,2005
[3]Knobbe E T,Dunn B,Fuqua P D,et al.Laser behavior and photostability characteristics of organic dye diped silicate gel materials[J].Applied Optics,1990,29:2729
[4]Dubois A,Callva M,Brun A,et al.Photostability of dye molecules trapped in solid materials [J].Applied Optics.1996,35:3139
[5]王婷婷,一种新型的树莓形状荧光二氧化硅颗粒及其颗粒膜的制备[A],2008,5
[6]Santra S,Wang K M,Tapec R,et al.Development of novel dye-doped silica nanoparticles for biomarker application[J].Biomed Opt.,2001,6:160
[7]Zhang P,Guo J H,Wang Y,et al.Incorporation of luminescent tris(bipyridine)ruthenium(Ⅱ)complex in mesoporous silica spheres and their spectroscopic and oxygen-sensing properties[J].Mater.Lett.,2002,53:400
[8]Kim T H,Li G,Park W H,et al.Sensor application of submicro-sized silica particle functionalized with hydroxyphenylbenzoxazole[J].Mol.Cryst.Liq.Cryst.,2006,445:185
[9]Zhang X Z,Yue Y H,Gao Z.Recent progress in the preparation and application research of mesoporous molecular sieve materials[J].Chem.Chinese Universities,2003,24:121
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