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研究生: 阮品崴
Ruan, Pin-Wei
論文名稱: 中孔洞二氧化矽包覆矽酸釓奈米殼作為螢光及MRI雙功能顯影劑
Mesoporous SiO2 coated Gd silicate nanoshells as fluorescent and MR imaging probes
指導教授: 葉晨聖
Yeh, Chen-Sheng
學位類別: 碩士
Master
系所名稱: 理學院 - 化學系
Department of Chemistry
論文出版年: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 66
中文關鍵詞: 奈米矽酸钆螢光顯影劑核磁共振顯影
外文關鍵詞: nano, gd silicate, fluorescent, MRI image
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  • 本研究開發出具有綠色螢光以及MRI顯影特性的矽酸釓螢光奈米殼(Gd silicate:FITC nanoshell),其粒徑大小約為50~60 nm,並將矽酸釓螢光奈米殼包覆ㄧ層20 nm中孔洞二氧化矽層(Gd silicate:FITC@mSiO2),提高其材料表面積達到高裝載或修飾藥物的能力。藉由螯合釓離子在其二氧化矽孔洞內,增強了其核磁共振造影顯影的能力,其材料除了表現了優異的T1顯影劑的能力,更發現我們的材料具有磁場敏感性,在較高的磁場能展現出強的T2顯影能力,在高磁場7T底下,其r2值相較於磁場3T下高出了4到5倍。進而開發螯合釓離子的中孔洞二氧化矽包覆矽酸釓螢光奈米殼(Gd3+ chelated Gd silicate:FITC@mSiO2)新型T1和T2雙顯影劑。
    另一方面藉由修飾MHI-148在中孔洞二氧化矽包覆矽酸釓螢光奈米殼表面,結合MHI-148有機分子,癌細胞會藉由有機陰離子傳輸縮氨酸管道(organic anion transporting peptides)將其攝入,使之具有近紅外光放光和標定癌細胞能力,達到同時具有核磁共振造影顯影和可穿透表皮組織近紅外光螢光的能力,這種利用雙顯影的標定功能,將能更準確的定位偵測體內癌細胞腫瘤位置。

    This study aim to develop new nanocomposite of Gd silicate:FITC nanoshell (50~60 nm) with fluorescence integration and MR imaging ability. Gd silicate:FITC nanoshell served as a core and further encapsulated within 20 nm mesoporous silica shell to fabricate Gd silicate:FITC@mSiO2, this modification increase the particle’s surface area and loading ability. Gd3+ was used to chelate the interior channels of mesoporous silica, resulting in Gd3+ chelated Gd silicate : FITC@mSiO2 nanoparticle. The existence of Gd3+ within the mesoporous silica channel, can promote the transverse r1 relaxivity.Most interestingly, the Gd-containing silicates have an advantage in serving as negative contrast agents with effective T2-shortening characteristics in strong fields. The transverse relaxivity (r2) values enlarged in 4-5 times as field increased from 3T to 7T. In animal MR imaging
    In addition, MHI-148 was conjugated with Gd silicate:FITC @mSiO2 nanoparticle, which can modify the particle with near-infrared(NIR) radiation and targeting cancer cells ability, The cancer-specific uptake and retention of MHI-148 is likely to be mediated by organic anion transporting peptides (OATPs). MHI-148 conjugated Gd silicate:FITC@mSiO2 nanoparticles were fabricated to display dual modalities expressing MR and optical imaging. Future application of NIR fluorescent and MR images in the clinical used could lead to important progress in the management of cancer patients on an individual basis.

    第一章 緒論 1-1. 奈米材料簡介.................................1 1-2. 奈米材料的特性................................2 1-3. 奈米材料應用於醫學診療.........................3 1-3-1. 光學生物分子探針.........................3 1-3-2. 核磁共振造影技術.........................5 1-4. 金屬矽酸鹽奈米材料的特性與應用...................8 1-5. 二氧化矽奈米材料的特性與應用......................12 1-6. 近紅外光螢光分子(七甲川花菁染料)的特性與應用..............16 第二章 實驗藥品與儀器設備 2-1. 實驗藥品........................................18 2-2. 儀器設備..........................................19 第三章 中孔洞二氧化矽包覆矽酸釓奈米殼之合成與應用 3-1. 研究動機與目的.................................22 3-2. 中孔洞二氧化矽包覆矽酸釓螢光奈米殼之合成.................24 3-2-1. 合成矽酸釓奈米殼(Gd silicate).............24 3-2-2. 合成矽酸釓螢光奈米殼(Gd silicate:FITC) ..........25 3-2-3. 合成表面修飾APTES的中孔洞二氧化矽包覆矽酸釓螢光奈米殼 (APTES treated Gd silicate:FITC@mSiO2).............25 3-2-4. 合成螯合釓離子的中孔洞二氧化矽包覆矽酸釓螢光奈米殼 (Gd3+ chelated Gd silicate:FITC@mSiO2)...............26 3-2-5. 合成表面修飾MHI-148的中孔洞二氧化矽包覆矽酸釓螢光奈米殼(MHI-148 conjugated Gd silicate:FITC@mSiO2).............27 3-2-6. 核磁共振顯影之顯影劑樣品製備...................28 3-2-7. 細胞毒性測試(MTT assay).................28 3-3. 實驗結果與討論 3-3-1. 矽酸釓奈米殼(Gd silicate)之材料分析.............30 3-3-2. 矽酸釓螢光奈米殼(Gd silicate:FITC) 之材料分析.......32 3-3-3. 中孔洞二氧化矽包覆矽酸釓螢光奈米殼 (Gd silicate:FITC@mSiO2) 之材料分析........................34 3-3-4. 表面修飾APTES的中孔洞二氧化矽包覆矽酸釓螢光奈米殼 (APTES treated Gd silicate:FITC@mSiO2) 之材料分析.........37 3-3-5. 螯合釓離子的中孔洞二氧化矽包覆矽酸釓螢光奈米殼 (Gd3+ chelated Gd silicate:FITC@mSiO¬2)之材料分析..........41 3-3-6. 螯合釓離子的中孔洞二氧化矽包覆矽酸釓螢光奈米殼 於核磁共振顯影(MRI)之效果..................45 3-3-7. 表面修飾MHI-148的中孔洞二氧化矽包覆矽酸釓螢光奈米殼(MHI-148 conjugated Gd silicate:FITC@mSiO¬2) 之材料分析........51 3-3-8. 表面修飾MHI-148的中孔洞二氧化矽包覆矽酸釓螢光奈米殼 (MHI-148 conjugated Gd silicate:FITC@mSiO¬2) 之毒性測試...56 3-3-9. 表面修飾MHI-148的中孔洞二氧化矽包覆矽酸釓螢光奈米殼(MHI-148 conjugated Gd silicate:FITC@mSiO¬2)體內螢光顯影....59 第四章 結論..................62 第五章 參考文獻.........................63

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