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研究生：	許綱哲 Hsu, Kang-Che
論文名稱：	生物降解性二氧化矽奈米管的製備與其在藥物輸送和磁共振照影之應用 Fabrication of Biodegradable Silica Nanotubes and Their Applications in Drug Delivery and MRI
指導教授：	葉晨聖 Yeh, Chen-Sheng
共同指導教授:	蘇世剛 Su, Shyh-Gang
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：	2010
畢業學年度：	98
語文別：	中文
論文頁數：	69
中文關鍵詞：	二氧化矽、奈米管、生物降解、藥物輸送、磁共振照影
外文關鍵詞：	silica, nanotube, biodegradation, drug delivery, MRI
相關次數：	點閱：113 下載：0
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在過去的數十年間，奈米尺寸的材料已經展現它在藥物傳輸平台上的前途。許多的研究已經顯示，很多的無法降解的無機材料，無論是否有經過修飾，對於人工培養的細胞或是動物模型都沒有毒害性的。即使如此，可以被人體排泄掉的生物降解性奈米材料，其發展還是受到醫護人員的高度期待。
在本篇研究中，製備出pH值依賴性降解的二氧化矽奈米管，該二氧化矽奈米管可以在水中溶解形成矽酸。二氧化矽奈米管可以抵抗酸性條件，但是在pH=8 環境下快速地降解。而且降解速率可以藉由改變二氧化矽奈米管的厚度來調控，越厚的的殼層其被溶解的速率越快。這個降解的特性使得二氧化矽奈米管具有扮演口服用藥載體的潛力。因為二氧化矽奈米材料很容易藉由表面修飾來衍生化，二氧化矽奈米管可以更進一步被開發成磁共振造影的顯影劑與藥物載體。經由腐蝕Gd(OH)3奈米棒而釋放出來的Gd3+離子，與預先修飾在二氧化矽的螯合劑DOTA錯合，生成DOTA-Gd接合之二氧化矽奈米管。最後，將接有DOTA-Gd之二氧化矽奈米管裝填抗癌藥物，可以同時展現出增顯的T1弛緩速率與抗癌活性。

In the past few decades, nanoscale materials have shown promise for drug delivery platform. Considerable studies have shown that many non-degradable inorganic nanomaterials are harmless to cultured cells or in animal models, either in nature or functionalized. However, the development of biodegradable nanomaterials, which can be excreted from
the human body, is still strongly anticipated by medical practitioners.
In this study, a pH-dependence of degradable silica nanotube is fabricated, which is dissolved to bodegradation product silicic acid in water. The silica nanotube is resistant to acidic condition, but degrades rapidly at pH 8. And the degradation rate can be tuned via tailoring the
shell thickness of silica nanotube, which is dissolved more slowly with thicker shell. This feature of degradation makes silica nanotube act as a potential oral-based administration carrier. Because silica-based materials
are readily functionalized via surface modification, silica nanotube can be further developed as MR imaging contrast agent as well as drug carrier. The realeased Gd3+ ions resulting from the etching of Gd(OH)3 nanorod are chelated by chelating agent DOTA, which is pre-modified on silica
nanotube, yielding DOTA-Gd grafted silica nanotube. Finally, the DOTA-Gd grafted silica nanotube which is loaded with anticancer drugs, show enhanced T1 relaxation and anticancer activity simultaneously.

第一章、緒論 ..............................................1 
1-1 奈米科學與技術 .........................................1 
1-2 奈米材料的特性 .........................................2 
1-2.1 尺寸效應 ........................................2 
1-2.2 表面效應 ........................................3 
1-2.3 量子效應 ........................................3 
1-2.4 奈米粒子的分散與聚集 .................................4 
1-3 二氧化矽奈米材料的合成與特性 ............................6 
1-3.1 二氧化矽奈米粒子合成與機制 ........................6 
1-3.2 不同反應參數對非晶形二氧化矽降解之影響 ..............7 
1-3.3 以模板製備二氧化矽奈米管狀材料 ....................10 
1-4奈米材料應用在藥物傳輸系統 ..............................15 
1-4.1 奈米藥物傳輸之發展 ..............................15 
1-4.2 二氧化矽奈米藥物載體 ..............................17 
1-5磁共振照影(magnetic resonance imaging，MRI) ...........22 
1-5.1 磁共振的基本原理 ................................22 
1-5.2 磁共振照影顯影劑(MRI contrast agent) ............24 

第二章、實驗部份 ..........................................26 
2-1 研究動機與目的 ........................................26 
2-2 實驗藥品 .............................................27 
2-3 儀器設備 .............................................29 
2-4 實驗流程 .............................................32 
2-5 奈米材料的合成 ........................................33 
2-5.1 氫氧化釓奈米棒(Gd(OH)3 nanorod)的製備 ...........33 
2-5.2 二氧化矽包覆之氫氧化釓奈米棒 .....................33 
2-5.3 二氧化矽層表面修飾氨基 ...........................33 
2-5.4 製備表面接有DOTA-Gd錯合物之二氧化矽奈米管(silica nanotube-DOTA-Gd，SNDG) ......................34 
2-6 樣品製備 ............................................34 
2-7 水中矽酸鹽檢測方法－鉬矽酸鹽比色法 ...... ..............35 
2-8 二氧化矽奈米管降解實驗 ................................35 
2-9 實驗細胞株 ..........................................36 
2-10 MTT細胞毒性檢驗 (MTT assay) .........................36 
2-11 奈米材料SNDG之MRI實驗 ................................37 
2-12 以雷射掃描共軛聚焦顯微鏡(LSCM)觀察以SNDG培養細胞之實驗 ...37 

第三章、結果與討論 ........................................38 
3-1 二氧化矽奈米管的性質與結構鑑定分析 ......................38 
3-2 二氧化矽奈米管在不同反應參數下的降解 ....................47 
3-3 二氧化矽奈米管在藥物釋放之測試 ..........................54 
3-4 SNDG(接有DOTA-Gd錯合物之二氧化矽奈米管)的細胞毒性測試 .....57 
3-5 SNDG(接有DOTA-Gd錯合物之二氧化矽奈米管)在MRI顯影之效果 ...58 
3-6 SNDG(接有DOTA-Gd錯合物之二氧化矽奈米管)作為載體在藥物傳輸上之應用 ................................................61 

第四章、結論 .............................................65 

參考文獻 ..............................................66

                                    

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校內：2011-07-22公開
校外：不公開電子論文尚未授權公開，紙本請查館藏目錄

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