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研究生: 吳佩臻
Wu, Pei-Jhen
論文名稱: 開發具有第三生物視窗光動力治療潛力的上轉換/富勒烯奈米複合材料
Development of Upconversion/C60 Hybrid Nanoparticles for Potential Photodynamic Therapy in Third Biological Window
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: 2020
畢業學年度: 108
語文別: 中文
論文頁數: 54
中文關鍵詞: 上轉換奈米粒子富勒烯光動力治療第三生物視窗
外文關鍵詞: upconversion nanoparticles, fullerene, photodynamic therapy, third biological window
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  • 目前面臨的挑戰包括進行較深層組織治療時,用來治療所使用的激發光源穿透深度是一大考驗,若使用紫外/可見光波長範圍的光源,可能會在組織體內產生散射導致光穿透深度較淺。因此我們想要開發第三生物視窗作為激發光源,在此波長能夠有較好的組織穿透深度並且能減少組織體內的光散射,是深層組織治療的理想選擇,因此利用摻雜鉺離子的上轉換奈米粒子作為吸收第三生物視窗的光。
    首先我們合成核-殼-殼上轉換奈米粒子(NaYF4:Er@NaYF4@NaYF4),可以看到覆蓋惰性殼層後,能夠有效避免活化劑 (Er3+) 擴散至外界環境導致螢光焠滅。接著我們使用逆微胞法將富勒烯和上轉換奈米粒子同時包覆在二氧化矽殼層中,當上轉換奈米粒子照射1550nm雷射後,會放出540nm綠光放光,然而富勒烯在波長532nm單態氧轉換效率很高,因此我們希望上轉換奈米粒子放出的綠光能夠藉由頻率共振能量轉移的方式來活化富勒烯,使其能夠有效產生單態氧以進行光動力治療。

    The present challenges included penetration depth of activating light as external trigger for smart nanodrugs for deeper tissue treatment. Ideally, NIR-III biological window (1550-1870 nm) had advantage of deeper tissue theragnostic considering the extended penetration depth and reducing light scattering. We provided NIR-III responsive Er3+ doped upconversion nanoparticles.
    First, we synthesized upconversion nanoparticles (NaYF4:Er@NaYF4@NaYF4). After coating the inert shell, it could protect the activator (Er3+) diffusing to outer surroundings. Thus, it could obviously enhance the intensity of fluorescence. We used reverse micelle sol-gel method to combined with upconversion nanoparticles and fullerene inside the silica shell simultaneously. We chose 1550 nm laser as the light source. Once irradiating the upconversion nanoparticles, it would generate emission at 540 nm. Fullerene had great singlet oxygen conversion efficiency at 532 nm. Thus, it could be activated by frequency resonance energy transfer (FRET) and generate efficient singlet oxygen for photodynamic therapy.

    摘要 I 英文延伸摘要(Extended Abstract) II 誌謝 X 目錄 1 圖目錄 4 表目錄 5 第一章、 緒論 6 1-1 上轉換材料簡介 6 1-1-1 上轉換材料組成 6 1-1-2 上轉換奈米粒子合成原理 8 1-1-3 上轉換機制 8 1-2 近紅外光生物視窗 9 1-3 光動力治療 11 1-3-1 光敏劑介紹 12 1-3-2 光敏劑之光化學機制 12 1-4 富勒烯光動力治療之應用 14 1-4-1 富勒烯簡介 14 1-4-2 富勒烯應用於光動力治療 14 1-5 上轉換材料結合富勒烯應用於光動力治療 16 第二章、 實驗藥品與儀器 21 2-1 實驗藥品 21 2-1-1 材料合成相關藥品 21 2-1-2 細胞實驗相關藥品 23 2-1-3 細胞實驗株 23 2-2 實驗儀器 24 2-2-1 材料鑑定儀器 24 2-2-2 細胞實驗儀器 25 第三章、 研究動機與實驗方法 26 3-1 研究動機 26 3-2 實驗方法 27 3-2-1 製備NaYF4:Er (core) 27 3-2-2 製備NaYF4:Er@ NaYF4 (core-shell) 28 3-2-3 製備NaYF4:Er@ NaYF4@ NaYF4 (core-shell-shell) 28 3-2-4 製備上轉換材料/富勒烯包覆二氧化矽殼層(UCNP/C60@SiO2) 29 3-2-5 上轉換材料/富勒烯奈米複合材料表面修飾(UCNP/C60@SiO2-APTES-PEG) 29 3-2-6 富勒烯包覆量測定 30 3-2-7 細胞活性實驗 30 3-2-8 單態氧測試 31 第四章、 實驗結果與討論 32 4-1 上轉換奈米材料之性質鑑定 32 4-1-1 比較摻雜不同鉺離子濃度之上轉換奈米材料螢光差異 32 4-1-2 探討摻雜不同鉺離子濃度之上轉換奈米材料形貌 33 4-1-3 比較不同惰性層厚度對螢光放光的影響 33 4-1-4 探討覆蓋不同惰性層層數的上轉換奈米材料形貌及螢光差異 36 4-1-5 覆蓋不同層數惰性層之上轉換材料形貌及鑑定 38 4-1-6 上轉換機制探討 41 4-2 上轉換/富勒烯奈米複合材料之性質鑑定 43 4-2-1 UCNP/C60@SiO2性質鑑定 43 4-2-2 UCNP/C60@SiO2-APTES-PEG性質鑑定 44 4-2-3 富勒烯包覆含量測定 47 4-3 細胞活性探討 48 4-4 探討單態氧釋放 49 第五章、 討論 50 第六章、 結論 51 參考文獻 52  

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