核甘酸與金屬離子可以藉由配位聚合的方式進行自組裝而製備出球狀膠體奈米粒子。此奈米粒子可透過包覆藥物分子及奈米尺度的載體提供多樣性的應用。在本研究中，將三磷酸腺苷修飾的超順磁性奈米粒子做為核並透過腺嘌呤與金離子以自組裝的方式在其外圍形成一不具晶形的保護層。自組裝的奈米粒子大小可經由反應時間、腺嘌呤濃度及金離子濃度之間的比例來完成。當腺嘌呤與金離子濃度比例為 1: 4時，經由穿透式電子顯微鏡鑑定結果其腺嘌呤/金奈米粒子之粒徑大小為140 nm 至 220 nm。此外，藉由載體自組裝過程中添加藥物或是染劑分子成功包覆於其中。本研究利用此新型自組裝藥物載體可應用於藥物傳輸系統，於細胞株 Tramp-C1 達到良好的治療效果。另外，研究中發現當加入1 mM 穀胱甘肽 (Glutathione)，發現酵素能有效的破壞載體結構而促使包覆內的藥物釋出，此具備控制與觸發應答性載體之特性於多項生醫領域中，具有良好且多功能的潛在前瞻性。

Nucleotides and metal ions could assemble spontaneously in water to form spherical colloidal particles through coordination polymerization. The encapsulation of guest molecules and nanoscale materials in these supramolecular networks holds promise to tailor their functions for various applications. In this work, adenosine 5’-triphosphate modified porous hollow superparamagnetic iron oxide nanoparticles (PHNPs) was served as a scaffold for defining assembly of the amorphous shell from adenine and gold ions. The size of the hybrid nanoparticles could be controlled by adjusting reaction conditions such as reaction time, concentration, and the ratio of reactants. Transmission electron microscopy results revealed the formation of hierarchical self-assembled nanoparticles in sizes ranging from 140 nm to 220 nm in diameter. Moreover, fluorescent dyes and drug molecules were also encapsulated successfully during the self-assembly process. When mixing with glutathione, an observable increase of florescence indicated the gradual release of guest molecules from the dye-incorporated hybrid nanoparticles. Triggered release was also accessible to high-frequency magnetic field change. Overall, the present hybrid nanoparticles provide versatile functionalities in a variety of applications. Their utilization in drug delivery and controlled release is currently in progress.

摘要 2
Abstract 3
致謝 4
總目錄 5
圖目錄 8
表目錄 10
第一章 緒論 11
1.1. 超分子化學奈米材料與生醫應用 11
1.1.1. 超分子化學簡介 11
1.1.2. 超分子-主體結構分類 12
1.1.3. 超分子－作用力分類 15
1.1.4. 生物性超分子材料 17
1.1.5. 鹼基類衍生物與金屬離子 18
1.1.6. 配位鍵超分子之合成機制 19
1.2. 生物型超分子材料於生醫領域上的應用 21
1.3. 研究目的與動機 22
第二章 實驗材料與方法 24
2.1. 實驗藥品與儀器 24
2.1.1. 實驗藥品 24
2.1.2. 緩衝溶液配製 25
2.1.3. 細胞培養與操作 26
2.1.4. 儀器 26
2.2. 奈米載體的合成與特性鑑定 27
2.2.1. 腺嘌呤/金奈米粒子合成 27
2.2.2. 修飾聚乙烯醇於adenine/ Au奈米粒子上 27
2.2.3. Adenine/ Au奈米粒子之加熱處理 28
2.3. 奈米藥物載體之合成與鑑定 28
2.3.1. 奈米載體載負藥物 28
2.3.2. 奈米藥物載體之載負效率定量 28
2.3.3. Adenine/ Au奈米藥物載體與榖胱甘肽的催化反應 28
2.4. 水溶性超順磁四氧化三鐵奈米粒子的合成與鑑定 29
2.4.1. 超順磁四氧化三鐵奈米粒子的合成 29
2.4.2. 將ATP修飾於四氧化三鐵奈米粒子的表面 30
2.4.3. 利用adenine/ Au將DOX及ATP/ PHNPs包覆於其中 30
2.4.4. Adenine/ Au奈米藥物載體與細胞的作用情形 31
第三章 實驗結果與討論 33
3.1. 奈米藥物載體的特性與鑑定 33
3.1.1. 奈米載體之粒徑大小和 Zeta 電位分析及光學特性 33
3.1.2. 奈米載體於生物緩衝溶液的穩定性 33
3.1.3. 加熱對於奈米載體的影響 34
3.1.4. PVA 對於奈米載體的影響 34
3.1.5. 最佳化奈米載體之特性鑑定 34
3.2. 奈米藥物載體的特性鑑定 35
3.2.1. 奈米藥物載體的特性鑑定 35
3.2.2. 奈米藥物載體的藥物飽和吸附量 35
3.2.3. 溶液條件下的藥物脫落分析 36
3.2.4. 奈米藥物載體的穀胱甘肽應答特性 36
3.3. 奈米藥物載體對細胞 Tramp-C1 的作用 37
3.3.1. 細胞存活率分析 37
3.3.2. 螢光顯微鏡影像 38
3.4. 超順磁性奈米載體的特性鑑定 38
3.4.1. 多孔性四氧化三鐵奈米粒子的特性鑑定 38
3.4.2. 三磷酸腺苷修飾 PHNPs 後的奈米粒子特性鑑定 38
3.5. 奈米載體包覆超順磁性奈米粒子的特性及應用 39
3.5.1. 包覆超順磁性奈米粒子對奈米載體本身的特性影響 39
3.5.2. 外加磁場對細胞吞噬奈米載體的影響 39
3.5.3. 奈米載體之核磁共振顯影的分析 40
第四章 結論 41
圖表說明 42
參考文獻 63

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