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研究生: 劉晏妮
Liu, Yan-Ni
論文名稱: NaYF4:Yb,Er近紅外光上轉換奈米粒子之製備及應用
Preparation and Application of NaYF4:Yb,Er Near-IR Upconversion Nanoparticles
指導教授: 陳東煌
Chen, Dong-Hwang
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 85
中文關鍵詞: 上轉換NaYF4:Yb,Er複合奈米粒子藥物釋放螢光顯影
外文關鍵詞: upconversion, NaYF4:Yb,Er, composite nanoparticles, drug release, fluorescence imaging
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  • 本論文係有關NaYF4:Yb,Er/二氧化矽/阿拉伯膠近紅外光上轉換複合奈米粒子之製備及作為兼具螢光顯影與藥物釋放功能之生醫奈米載體的應用研究。關於其製備,首先利用奧士瓦熟成法合成NaYF4:Yb,Er奈米粒子,接著以溶凝膠法在逆微胞系統中被覆二氧化矽奈米殼層在NaYF4:Yb,Er奈米粒子表面,製得NaYF4:Yb,Er-SiO2核殼型奈米粒子(NaYF4:Yb,Er@SiO2)。接著,以(3-氨基丙基)三乙氧基矽烷將二氧化矽表面修飾成具有氨基,最後再將阿拉伯膠(GA)以碳二醯胺活化法接枝在氨基化之二氧化矽表面,製得阿拉伯膠修飾之NaYF4:Yb,Er@SiO2複合奈米粒子(NaYF4:Yb,Er@SiO2@GA)。透過利用穿透式電子顯微鏡(TEM)、高解析電子顯微鏡(HR-TEM)、X光繞射分析、傅立葉轉換紅外光(FIIR)光譜、界面電位(zeta potential)、及紫外光/可見光/近紅外光光譜(UV/VIS/NIR)分析產物之粒子形態、粒徑、晶體結構、界面電位及光學性質,可證實本研究成功製備出NaYF4:Yb,Er@SiO2@GA複合奈米粒子。將此NaYF4:Yb,Er@SiO2@GA複合奈米粒子作為藥物載體,發現它們並無顯著的生物毒性,但在負載抗癌藥物DOX後,可有效毒殺人類子宮頸癌細胞。此外,以近紅外雷射照射,它們因近紅外光上轉換特性亦可發出可見光螢光。如此,本研究所製備之NaYF4:Yb,Er@SiO2@GA複合奈米粒子兼具螢光生物顯影與藥物釋放的功能,預期在生醫應用上甚具潛力。

    This thesis concerns the fabrication of NaYF4:Yb,Er/silica/gum arabic near-IR up-conversion composite nanoparticles and their application as a biomedical nanocarrier with the functions of bio-imaging and drug release simultaneously. For their fabrication, NaYF4:Yb,Er nanoparticles were obtained by ostwald ripening method at first. Then, SiO2 nanoshells were coated on NaYF4:Yb,Er nanoparticles by sol gel method in a reverse micellar system to yield the NaYF4:Yb,Er-SiO2 core-shell nanoparticles (NaYF4:Yb,Er@SiO2). After modification with (3-Aminopropyl)triethoxysilane to generate amino groups on the surface of SiO2 nanoshell, gum arabics (GA) were grafted onto the amino-functionalized surface of SiO2 via carbodiimide activation to form the GA-modified NaYF4:Yb,Er@SiO2 composite nanoparticles (NaYF4:Yb,Er@SiO2@GA). From the characterization of morphology, size, structure, functional group, zeta potential, and optical property by TEM, HR-TEM, XRD, RTIR, zeta potential, and UV/VIS/NIR spectrum, the successful fabrication of NaYF4:Yb,Er@SiO2@GA composite nanoparticles has been demonstrated. The NaYF4:Yb,Er@SiO2@GA composite nanoparticles were used as the drug carrier. It was found that they had no significant cytotoxicity but could kill the HeLa cells effectively after loading with the anti-cancer drug doxorubicin (DOX). Furthermore, they also could emit visible fluorescence while exposed to a near-IR laser owing to the near-IR up-conversion property. Thus, the resultant NaYF4:Yb,Er@SiO2@GA composite nanoparticles had the functions of fluorescence bio-imaging and drug release simultaneously and were expected to have great potential in the biomedical application.

    中文摘要…………………………………………………………… I 英文摘要…………………………………………………………… II 誌謝………………………………………………………………… III 總目錄……………………………………………………………… IV 表目錄……………………………………………………………… VII 圖目錄……………………………………………………………… VIII 第一章 緒論…………………………………………………… 1 1.1 上轉換材料簡介……………………………………………… 1 1.2 NaYF4:Yb,Er奈米粒子…………………………………… 3 1.2.1 NaYF4:Yb,Er奈米粒子之晶體結構與性質………… 3 1.2.2 NaYF4:Yb,Er奈米粒子之製備……………………… 6 1.2.3 NaYF4:Yb,Er奈米材料之表面改質………………… 11 1.2.4 NaYF4:Yb,Er奈米粒子之應用……………………… 12 1.2.5 NaYF4:Yb,Er@SiO2奈米粒子之生物相容性……… 17 1.3 阿拉伯膠…………………………………………………… 18 1.4研究動機……………………………………………………… 20 第二章 理論基礎……………………………………………… 21 2.1上轉換原理…………………………………………………… 21 2.1.1概述……………………………………………………… 21 2.1.2 NaYF4:Yb,Er奈米粒子之上轉換原理……………… 23 2.2二氧化矽之合成與表面改質………………………………… 25 2.2.1二氧化矽之合成………………………………………… 25 2.2.2二氧化矽之表面改質…………………………………… 29 2.3藥物釋放技術………………………………………………… 30 2.3.1 概述…………………………………………………… 30 2.3.2奈米藥物載體…………………………………………… 31 第三章 實驗方法……………………………………………… 34 3.1實驗藥品、儀器及材料……………………………………… 34 3.1.1實驗藥品………………………………………………… 34 3.1.2 實驗儀器……………………………………………… 35 3.1.3 實驗材料……………………………………………… 36 3.1.4 實驗細胞株…………………………………………… 36 3.2製備方法……………………………………………………… 37 3.2.1 NaYF4:Yb,Er奈米粒子之製備……………………… 37 3.2.2二氧化矽包覆NaYF4:Yb,Er奈米粒子之製備………… 37 3.2.3阿拉伯膠包覆表面改質氨基二氧化矽殼層包覆 NaYF4:Yb,Er複合型奈米粒子之製備………………… 41 3.3性質測定與分析……………………………………………… 44 3.4 NaYF4:Yb,Er/二氧化矽/阿拉伯膠複合奈米粒子作為藥物載 體之應用……………………………………………………… 46 3.5結合抗癌藥物Doxorubicin之NaYF4:Yb,Er/二氧化矽/ 阿拉伯膠複合奈米載體在體外試驗中之癌細胞毒殺研究……… 47 第四章 結果與討論…………………………………………… 49 4.1 NaYF4:Yb,Er/二氧化矽/阿拉伯膠複合奈米粒子之材料性質 特性分析……………………………………………………… 49 4.1.1粒子形態與粒徑大小…………………………………… 49 4.1.2晶相結構………………………………………………… 53 4.1.3 鍵結型態…………………………………………………57 4.1.4界面電位與等電點..…………………………………… 60 4.1.5光學性質………………………………………………… 63 4.2 NaYF4:Yb,Er/二氧化矽/阿拉伯膠複合奈米粒子作為藥物載 體之研究…………………………………………………………67 4.2.1抗癌藥物Doxorubicin在NaYF4:Yb,Er/二氧化矽/ 阿拉伯膠複合奈米粒子上之吸附與釋放研究………… 67 4.2.2 NaYF4:Yb,Er/二氧化矽/阿拉伯膠複合奈米粒子於人類 子宮頸癌細胞 (HeLa cells)顯影功能之研究……… 72 4.2.3結合抗癌藥物Doxorubicin之NaYF4:Yb,Er/二氧化矽/ 阿拉伯膠複合奈米粒子於人類子宮頸癌細胞 (HeLa cells)毒殺功能之研究………………………… 74 第五章 總結論……………………………………………………79 參考文獻…………………………………………………………… 81 自述………………………………………………………………… 85

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