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研究生:廖智盛
研究生(外文):Zhi-Sheng Liao
論文名稱:高度敏感性酸鹼應答型高分子微胞應用於高效抗癌治療及可控制的藥物傳輸
論文名稱(外文):Ultrasensitive pH-Responsive Polymeric Micelles for High-Efficiency Anticancer Therapy and Controllable Drug Delivery
指導教授:鄭智嘉
指導教授(外文):Chih-Chia Cheng
口試委員:邱信程謝永堂高震宇陳建光蔡協致何郡軒鄭智嘉
口試委員(外文):Hsin-Cheng ChiuYeong-Tarng ShiehChen-Yu KaoJem-Kun ChenHsieh-Chih TsaiJinn-Hsuan HoChih-Chia Cheng
口試日期:2017-07-04
學位類別:碩士
校院名稱:國立臺灣科技大學
系所名稱:應用科技研究所
學門:自然科學學門
學類:其他自然科學學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:106
中文關鍵詞:高度酸鹼應答聚胺酯共聚高分子高度微胞穩定性藥物釋放抗癌治療
外文關鍵詞:Ultrasensitive pH-ResponsivePolyurethaneHighly micelles stabilityDrug releaseAnti-cancer therapies
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本研究成功合成出具備高度酸鹼應答能力的聚胺酯共聚高分子,此材料不僅能在水溶液中自組裝形成奈米尺寸的微胞,且具有優異的藥物負載能力及可調控的藥物包覆量,於長效測試中亦呈現出高度微胞穩定性。在小鼠巨噬細胞(Raw 264.7)的體外實驗,不僅能成功透過環境酸鹼值控制藥物釋放的行為,更能在微酸環境條件下(pH = 6.0)觀測到藥物胞吞作用(Endocytosis)的過程,證實此材料不僅有極優越的藥物釋放能力,且有機會拓展至人體抗癌治療的發展潛力。
This work has successfully constructed a polyurethane containing Ultrasensitive pH-Responsive ability. The new material can not only perform self-assembly of nano-scale micelles in aqueous solution, but also possess excellent drug-loading capability and adjustable drug-loading capacity. Besides, in the test of a long period of time, the micelles still represent highly durability and stability. In vitro test of the Macrophages (Raw 264.7), the behavior of the drug release can be well controlled by the pH value of the environment. Moreover, under weak acidic conditions (pH = 6.0), endocytosis was observed, which prove that this material not only shows promising drug release ability, but also has potentials in expanding to the anti-cancer therapies in human bodies.
摘要
Abstract
致謝
目錄
表目錄
圖目錄
縮減表
第一章 緒論
1.1研究背景
1.2研究動機
第二章 文獻回顧
2.1阿黴素(Doxorubicin,Dox)
2.2聚胺酯(Polyurethane, PU)
2.3聚乙二醇(Polyethylene glycol,PEG)
2.4點擊化學(Click Chemistry)
2.5高分子奈米載體(Polymeric nanoparticles)
2.6雙親性高分子微胞(amphiphilic block copolymer Micelles)
2.7刺激應答 (Stimuli-Responsivenesss)
第三章 實驗材料與方法
3.1研究設計
3.2實驗材料
3.2.1實驗藥品
3.2.2實驗溶劑
3.2.3細胞實驗材料
3.2.4相關實驗材料
3.3實驗儀器與設備參數
3.3.1旋轉塗佈機(Spin Coaters)
3.3.2桌上型酸鹼度計(pH Meter)
3.3.3酵素免疫分析儀(ELISA Reader)
3.3.4高效能凍乾機(Freeze dryer)
3.3.5 CO2培養箱(CO2 incubators)
3.3.6抽屜式UV機(Drawer UV machine)
3.3.7冷凍離心機(Refrigerated Centrifuge)
3.3.8斜式旋轉濃縮機(Rotary Evaporation)
3.3.9流式細胞分選儀(Flow Cytometers)
3.3.10振盪混合器(Vortex Mixer)
3.3.11光致螢光光譜儀(Photoluminescence, PL)
3.3.12光學視頻接觸角量測儀(Contact angle)
3.3.13熱重分析儀(Thermogravimetric analysis,TGA)
3.3.14紫外線光譜儀(UV/VIis spectrophotometer ,UV/Vis)
3.3.15凝膠滲透層析儀(Gel permeation chromatography,GPC)
3.3.16螢光顯微鏡(Fluorescence microscope)
3.3.17原子力顯微鏡(Atomic Force Microscpoic,AFM)
3.3.18奈米粒徑分析儀(Dynamic Light Scattering,DLS)
3.3.19差示掃描量熱儀(Differential scanning calorimetry,DSC)
3.3.20高解析度場發射掃描式電子顯微鏡(Scanning Electron Microscope)
3.3.21傅里葉轉換紅外光譜(Fourier transform infrared spectroscopy) 35
3.3.22液態核磁共振光譜(Nuclear Magnetic Resonance Spectrometer,NMR)
3.3.23穿透式電子顯微鏡(Transmission electron microscope,TEM)
3.4實驗合成步驟
3.4.1合成Poly(propylene glycol)- Azide(PPG - N3)
3.4.2合成 Alkyne-functionalized polyethylene glycol(PEG - alkyne)
3.4.3合成Azide-functionalized Polyurethane(PU - N3)
3.4.4合成 Polyurethane - Polyethylene glycol(PU - PEG)
3.5樣品製備
3.6細胞生物性製備
第四章 結果與討論
4.1 材料鑑定
4.1.1 傅里葉轉換紅外光譜FTIR
4.1.2 核磁共振氫譜1H NMR
4.1.3 凝膠滲透層析儀GPC
4.1.4 熱重分析儀TGA
4.1.5 熱差式分析儀DSC
4.1.6 光學接觸角Contact Angle
4.2 材料性質分析
4.2.1 臨界微胞濃度CMC
4.2.2 粒徑分析DLS
4.2.3 微胞穩定性分析
4.2.4 環境刺激響應測試
4.3藥物微胞分析
4.3.1藥物包覆率與粒徑分布
4.3.2藥物微胞穩定性分析
4.3.3掃描電子顯微鏡SEM、穿透式電子顯微鏡TEM、原子力顯微鏡AFM
4.3.4體外藥物釋放Drug release in vitro
4.3.5 細胞毒性測試Cytotoxicity test
4.3.6螢光顯微鏡CLSM
4.3.7流式細胞儀Flow cytometer
第五章 結論
第六章 未來展望
第七章 參考文獻
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