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研究生： 蕭義勳
Shiao, Yi-Syun
論文名稱： 適體修飾之金奈米粒子於癌症標靶治療之應用
Aptamer Functionalized Gold Nanoparticles for Targeted Cancer Therapy
指導教授： 黃郁棻
口試委員: 孫毓璋
黃志清
學位類別： 碩士
Master
系所名稱： 原子科學院 - 生醫工程與環境科學系
Department of Biomedical Engineering and Environmental Sciences
論文出版年： 2011
畢業學年度： 100
語文別： 中文
論文頁數： 71
中文關鍵詞： 適體 、金奈米粒子 、癌症治療
外文關鍵詞： Aptamer, Gold nanoparticles, Cancer therapy
相關次數： 點閱：3  下載：0 
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    • 本研究主要利用金奈米粒子 (Gold nanoparticle, Au NP) 結合一雙股結構之核酸適體ds(sgc8c)，開發成新穎之奈米藥物載體，應用於癌細胞的標靶治療。ds(sgc8c)中的適體結構 (sgc8c aptamer)，可用來辨識跨膜蛋白 (Transmembrane protein)─protein tyrosine kinase 7 (PTK7)，此蛋白在急性淋巴型T細胞白血病 (Acute lymphoblastic leukemia, ALL) 的癌細胞株CCRF-CEM細胞膜表面，有高度的表現量。此外由適體結構延伸而出的雙股核酸 (DNA) 序列，含有連續且重複的CG鹼基對，能嵌合 (Intercalation) 數個化療藥物「小紅莓」(Doxorubicin) 分子。定量結果顯示，一顆粒徑為13奈米的金粒子表面，可修飾61 ± 10條雙股DNA，以及280 ± 23個Doxorubicin分子，具有良好的載藥效率。本研究開發的奈米藥物載體，能藉由適體與目標細胞進行專一性作用，降低抗癌藥物對非目標細胞的毒性；此藥物載體平台系統，亦可依據特定癌細胞株，搭配不同適體，應用於多種癌細胞之標靶治療。

    摘要 I Abstract II 謝誌 III 總目錄 IV 圖目錄 VII 表目錄 IX 第一章 序論 1 1.1 癌症與治療 1 1.1.1癌症 1 1.1.2白血病 1 1.1.3臨床上的治療方式 2 1.1.4癌症化學療法 4 1.2 生醫奈米材料的應用 8 1.2.1 生醫奈米材料 8 1.2.2 金奈米粒子之應用 12 1.3 癌症之標靶治療 15 1.4 核苷酸序列結合奈米粒子的應用 20 1.4.1以金奈米粒子穩定DNA 20 1.4.2奈米粒子與DNA在藥物傳遞和顯影技術上的發展 21 1.5 研究動機與目的 27 第二章 材料與方法 32 2.1 實驗藥品 32 2.2 奈米藥物載體的合成 32 2.2.1 合成13-nm之金奈米粒子 32 2.2.2 設計DNA 鹼基序列 33 2.2.3 將dsDNA修飾於金奈米粒子表面 34 2.2.4 裝載化療藥物 35 2.3 奈米藥物載體的特性鑑定 35 2.3.1 ds(control) 半溶解溫度 (Tm) 的量測 35 2.3.2 ds(sgc8c) 的定量分析 36 2.3.3 藥物載體之電位 (zeta potential) 分析 36 2.3.4 藥物載體與化療藥物之親和性量測 37 2.3.5 藥物載體之穩定度測定 37 2.4 細胞培養步驟 37 2.4.1 細胞培養基配製 37 2.4.2 人類急性白血癌細胞的培養 38 2.5 以藥物載體進行癌症治療 38 2.5.1 利用流式細胞儀測定藥物載體標定能力 38 2.5.2 暗視野顯微鏡觀測細胞與藥物載體的作用 39 2.5.3 測定細胞對金奈米粒子的吞噬量 40 2.5.4 癌細胞存活率分析 41 第三章 結果與討論 42 3.1 藥物載體與藥物的作用 42 3.1.1 Dox穩定dsDNA的結構 42 3.1.2 藉由金奈米粒子提升dsDNA與Dox的親和性 42 3.2 以金奈米粒子為基礎之載體性質的合成與鑑定 45 3.2.1 藥物載體的合成與dsDNA修飾量 45 3.2.2 藥物載體之光學特性與飽和藥物承載量 46 3.2.3 藥物載體之水合半徑和Zeta電位分析 46 3.3 藥物載體與目標細胞CCRF-CEM之專一性作用 48 3.3.1 載體與目標細胞的標靶性與親和能力 48 3.4 藥物經載體傳遞與細胞的反應分析 51 3.4.1 不同細胞株的毒性試驗 51 3.4.2 不同細胞株的藥物螢光反應 52 第四章 結論 54 參考文獻 64

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