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研究生: 謝佳晉
Hsieh, Chia-Ching
論文名稱: 以第三生物視窗之1550 nm雷射激發二氧化矽披覆LiYbF4:Er@LiGdF4上轉換奈米粒子進行雙光動力治療
1550 nm Laser of the Third Biological Window Exciting Silica Coated LiYbF4:Er@LiGdF4 Upconversion Nanoparticles to Perform Dual Photodynamic Therapy
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: 2019
畢業學年度: 107
語文別: 中文
論文頁數: 51
中文關鍵詞: 上轉換第三生物視窗雙光動力治療
外文關鍵詞: upconversion, third biological window, dual photodynamic therapy
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  • 光動力治療為一新興的治療癌症方法,不僅提供良好的治療效果,更能有效的減少副作用產生,然而,光動力治療在發展上一直受限於光敏劑的吸收波長,意即光敏劑能夠吸收之波段的光,其穿透深度不佳,容易被組織吸收,造成應用上的阻礙,因此,本研究透過結合上轉換奈米粒子與兩種光敏劑,從而得以進行穿透度深的雙光動力治療。首先我們合成出核殼上轉換奈米粒子─LiYbF4:Er@LiGdF4,透過披覆二氧化矽殼層將材料轉成親水性質,並將光敏劑Rose Bengal 和Chlorin e6 修飾於上轉換奈米粒子上,隨後以位於第三生物視窗,具有良好穿透深度之1550 nm 雷射作為入射光源,藉由材料之上轉換特性,吸收1550 nm 激發光並釋放可見光,再由兩種光敏劑分別吸收由材料釋放之可見光,經由螢光共振能量轉移(fluorescence resonance energy transfer, FRET)產生活性氧物質(reactive oxygen species, ROS),利用ROS毒殺癌細胞,進行雙光動治療。

    Photodynamic therapy (PDT) has been emerging as a therapeutic modality featuring microtrauma, low toxicity, favorable selectivity and less side effects in tumor treatment. However, the further development of PDT was largely limited by the potency of the photosensitizer. Most conventional photosensitizers used in PDT are excited by ultraviolet to visible (UV-Vis) light, which suffers from poor tissue penetration depth and UV light hazards in patients. Therefore, we utilized the lanthanide doped upconversion nanoparticles (UCNPs)─LiYbF4:Er@LiGdF4 in PDT. Due to the specific property of upconversion, UCNPs are capable of converting near infrared (NIR) light into UV-visible light, which can activate photosensitizers. This is achieved by coating silica shell around the nanoparticles, transferred UCNPs from hydrophobic into hydrophilic. And then modifying photosensitizers, Rose Bengal and Chlorin e6, on the silica matrix. Upon irradiation with 1550 nm laser which is located at third biological window can provide deep penetration for dual photodynamic therapy. The photosensitizer would produce reactive oxygen species (ROS) through fluorescence resonance energy transfer (FRET) inducing tumor cells apoptosis. Notably, the good therapeutic efficiency and less side effects of dual photodynamic therapy imply that it is a potential candidate for clinical application.

    摘要 I Extended Abstract II 誌謝 XIII 目錄 XIV 圖目錄 XVI 表目錄 XX 第壹章、緒論 1 1.1 奈米科技 1 1.2 上轉換奈米材料簡介 2 1.3 上轉換奈米粒子─主體晶格與摻雜 2 1.4 上轉換奈米粒子之光學機制 4 1.5 上轉換奈米粒子合成 6 1.6 上轉換奈米粒子─LiYbF4 : Er介紹 7 1.7 二氧化矽包覆上轉換奈米粒子 8 1.8 光動力治療 10 1.9 上轉換奈米粒子於光動力治療應用 10 1.10 第三生物視窗 12 第貳章、實驗藥品與儀器 13 2.1 合成UCNPs@SiO2-RB-Ce6所需要藥品 13 2.2 實驗儀器 14 第參章、研究動機與實驗步驟 16 3.1 研究動機 16 3.2 實驗步驟 17 3.2.1 合成LiYbF4:Er核奈米粒子(Core Nanoparticles) 17 3.2.2 合成LiYbF4:Er@LiGdF4核殼奈米粒子(Core shell Nanoparticles) 18 3.2.3 披覆二氧化矽殼於上轉換核殼奈米粒子(UCNPs@SiO2) 19 3.2.4 以3-氨基丙基三乙氧基矽烷(APTES)修飾胺基於二氧化矽披覆核殼上轉換奈米粒子(UCNPs@SiO2-NH2) 20 3.2.5 將孟加拉玫瑰紅(Rose Bengal)修飾於UCNPs@SiO2-NH2表面 21 3.2.6 將二氫卟吩(Chlorin e6)修飾於UCNPs@SiO2-NH2表面 21 3.2.7 將孟加拉玫瑰紅與二氫卟吩修飾於UCNPs@SiO2-NH2表面 22 3.2.8 以二氧化矽殼層包覆孟加拉玫瑰紅於上轉換核殼奈米粒子並修飾上二氫卟吩(UCNPs@SiO2(RB)-Ce6) 23 第肆章、實驗結果與討論 25 4.1 LiYbF4:Er核奈米粒子之結構與光學性質探討 25 4.2 LiYbF4:Er@LiGdF4核殼奈米粒子之結構與光學性質探討 28 4.3 UCNPs@SiO2與UCNPs@SiO2-NH2之鑑定和光學性質探討 33 4.4 修飾光敏劑─孟加拉玫瑰紅與二氫卟吩(RB、Ce6)後的材料鑑定和光學性質探討 35 4.4.1 修飾光敏劑─孟加拉玫瑰紅(Rose Bengal, RB) 35 4.4.2 修飾光敏劑─二氫卟吩(Chlorin e6, Ce6) 40 4.4.3 修飾光敏劑─孟加拉玫瑰紅和二氫卟吩(Rose Bengal, RB和 Chlorin e6, Ce6) 44 第伍章、結論 47 參考文獻 48

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