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  • 學位論文

多功能磁共振顯影劑在生物上之應用

Multifunctional Magnetic Resonance Imaging Contrast Agents for Biological Application

指導教授 : 牟中原

摘要


近年來磁共振造影已成為醫療診斷上重要的工具之一,其中磁共振顯影劑方面的研究更是此領域相當重要的一部分,隨著奈米科技臻於成熟,因此開發個人化的奈米粒子顯影劑,儼然已成為科學家們所共同努力的目標。本研究主要分為兩部分,第一部分為利用熱分解方法合成錳鐵雙金屬氧化物奈米粒子,透過穿透式電子顯微鏡、超導量子干涉儀、感應耦合電漿質譜儀及X光粉末繞射儀鑑定其組成及結構,為了進一步於生物上之應用,於此奈米粒子表面包覆一層二氧化矽殼層,並可同時包覆螢光劑於此殼層內達成雙功能(磁性和螢光)的奈米粒子。活體之應用為將此奈米粒子以尾靜脈方式送入大鼠體內,以進行磁共振顯影的實驗,結果顯示,於腦內之海馬迴、腦垂體、小腦、下顎腺以及腎臟皆有明顯之顯影效果,其原因也詳細地探討。   第二部分為利用四氧化三鐵包附上具有中孔洞二氧化矽的奈米粒子,同時可將螢光劑鑲嵌於此二氧化矽的結構中以合成三功能(磁性、螢光和中孔洞)之奈米粒子。細胞實驗測試中,此奈米粒子具有高度的生物相容性且證實可進入細胞,利用流式細胞儀和磁共振顯影可得到高度的標的效率和明顯之影像對比效果。以上結果證實此多功能奈米粒子於細胞標的以及細胞追蹤上極具潛力。

並列摘要


In recent years, magnetic resonance imaging (MRI) plays an important role in bioimaging. Therefore, magnetic nanoparticles have attracted much attention as MRI contrast agents. Herein, we report a core shell bifunctional nanoparticle, MIO@SiO2-RITC (core: manganese iron oxide, MIO; shell: amorphous silica conjugated with RITC) with both fluorescent and magnetic properties for MR imaging. By tuning iron to manganese ratio, the nanoparticles possessed different saturated magnetization and relaxivities. SiO2 was selected for surface coating of IMO nanoparticles because dye molecules can be easily incorporated into silica shell. In addition, silica is quite biocompatible. The nanoparticles were characterized by TEM, ICP-MS, XRD and SQUID. In vivo MRI examination showed that contrast was enhanced in hippocampus, cerebellum, pituitary, submaxillary gland and kidneys of a rat in T1-weighted images, 72 h after tail vein injection. Cell labeling is also an important field in the biomaterials application. For that purpose, we report another T2 contrast agent mFe3O4@MSN-RITC, having multiple magnetite nanoparticles attatched to a mesoporous silica nanoparticle, and simultaneously, the dye molecules conjugated into the mesoporous silica framework. The tri-functional nanoparticles possess magnetic, fluorescent property, and large surface area. In vitro examination, the cell uptake efficiency and cytotoxicity was evaluated by flow cytometry, fluorescence microscopy and WST assay. The results showed that the nanoparticles have high biocompatibility and uptake efficiency.

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