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研究生: 陳柏瑋
Chen, Bo-Wei
論文名稱: 葡聚醣磁性奈米粒子之官能基修飾及生醫應用
Functional Groups Modification of Dextran-coated Magnetic Nanoparticles for Biomedical Applications
指導教授: 衛榮漢
Wei, Zung-Hang
口試委員: 李昇憲
黃育綸
劉博滔
學位類別: 碩士
Master
系所名稱: 工學院 - 奈米工程與微系統研究所
Institute of NanoEngineering and MicroSystems
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 97
中文關鍵詞: 四氧化三鐵磁性奈米粒子葡聚醣官能基修飾
外文關鍵詞: dextran, modifications
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  • 本計畫書旨在製備不同官能基修飾之葡聚醣包覆磁性氧化鐵奈米粒子,後欲將其及應用於生物醫學領域。由於葡聚醣於生物醫學上不會對細胞產生生物毒性,因此不會受到細胞排斥,因此葡聚醣適合應用於生物醫學領域。
    實驗上先以共沉法製備無修飾之磁性奈米粒子,並以物理性研磨的方式使葡聚醣能夠均勻包覆在磁性奈米粒子表面,再採用不同化學反應修飾不同種官能基(包含:氨基(-NH2)、羧基(-COOH)以及羥基(-OH))到葡聚醣包覆之磁性奈米粒子表面,使磁性奈米粒子分別具有的官能基。
    材料分析部分,使用超導量子干涉磁量儀(Superconducting quantum interference device,SQUID)、穿透式電子顯微鏡(Transmission electron microscope, TEM)及霍氏轉換紅外光譜儀 (Fourier transform infrared spectroscopy,FTIR)分別進行磁性奈米粒子的磁性、大小及表面修飾官能基的鑑定。藉由熱重分析儀(Thermogravimetric analysis,TGA)確認磁性奈米顆粒的葡聚醣包覆率以及官能基修飾量,並以熱示差描熱卡量計(Differential scanning calorimetry,DSC)獲知相變化的焓變化量。
    此外,將實驗室上屆畢業生黃俊榮學長研發之3-(3.4-羥基苯基)丙酸(3-(3,4-Dihydroxy)hydrocinnamic acid,DHCA)包覆四氧化三鐵進行抗癌藥物-帝盟多(Temozolomide,TMZ)修飾反應,利用DHCA提供之羧基官能基與TMZ鍵結,獲得抗癌藥物包覆之四氧化三鐵。再利用紫外光-可見光光譜儀(UV-vis spectrometer)檢測TMZ是否存在於顆粒表面,以證明藥物是否修飾成功。


      Dextran molecules with low bio-toxicity is beneficial for biomedical fields. Dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) can have broader applications if modified with different functional groups. Therefore, the aim of the thesis is to synthesiz iron oxide nanoparticles with functional groups for biomedical appications.
      Iron oxide nanoparticles (Fe3O4) were prepared by co-precipitation method and mixed with dextran solution under ball milling conditions to minimum particles size and assist dextran capping on particle surface. Different functional groups including amino (-NH2), carboxyl (-COOH) and hydroxyl groups (-OH) were then modified to dextran- Fe3O4 utilizing different chemical reactions. Superconducting quantum interference device (SQUID) and transmission electron microscope (TEM) were used to characterize and prove the superparamagnetism, size and shape. Fourier transform infrared spectroscopy (FTIR) analyzed the presence of functional groups. Thermogravimetric analysis (TGA) confirmed the mass percent of dextran and functional groups on iron oxide nanoparticles and phase transition enthalpy was determined by differential scanning calorimetry (DSC).
      Lastly, anti-cancer drugs, Temozolomide (TMZ), was modified on to the carboxyl groups of 3-(3,4-Dihydroxy)hydrocinnamic acid (DHCA) coated Fe3O4. UV-vis spectrometer was used to analyze the presence of TMZ on the particles and prove the successful modification.

    中文摘要 I Abstract II 致謝 III 目錄 IV 圖目錄 VII 表目錄 XII 第一章 緒論 1 1-1 前言 1 1-2 研究動機與目的 3 第二章 理論基礎及文獻回顧 4 2-1 奈米材料簡介 4 2-1-1 奈米材料之特性 4 2-2磁性材料之磁性理論 6 2-2-1 鐵磁性材料分類 6 2-2-2 磁滯現象 9 2-3磁奈米粒子特性 10 2-3-1 超順磁性 10 2-3-2 單磁區 12 2-4 葡聚醣包覆磁奈米顆粒合成及應用 13 2-4-1 界面活性劑之分散機制 14 2-4-2 葡聚醣包覆超順磁奈米氧化鐵之修飾 18 2-4-3 超順磁氧化鐵奈米粒子之應用 21 2-4-4 葡聚醣磁奈米粒子修飾藥物及其應用 22 第三章 實驗材料與方法 26 3-1 實驗架構 26 3-2 化學藥品 26 3-3 合成儀器架構 27 3-4 實驗步驟 28 3-4-1 共沉法製備葡聚醣包覆四氧化三鐵奈米粒子 28 3-4-2修飾官能基於葡聚醣包覆四氧化三鐵奈米粒子 28 3-4-3合成3-(3.4-羥基苯基)丙酸包覆四氧化三鐵奈米粒子 30 3-4-4修飾抗癌藥物Temozolomide (TMZ)於DHCA包覆四氧化三鐵奈米粒子 31 3-5 特性分析儀器 32 3-5-1 超導量子干涉磁量儀 (Superconducting Quantum Interference Device,SQUID) 32 3-5-2 穿透式電子顯微鏡 (Transmission Electron Microscope,TEM) 32 3-5-3 霍氏轉換紅外光譜儀 (Fourier Transform Infrared Spectroscopy,FTIR) 32 3-4-4 熱分析儀(Thermal Analyzer) 32 3-5-5 X光粉末繞射儀(X-Ray Powder Diffractometer,XRD) 33 3-5-6感應耦合電漿原子發射光譜分析儀(Inductivity Coupled Plasma - Atomic Emission Spectrometer,ICP-AES) 33 3-5-7 三維奈米拉曼螢光顯微鏡系統 (3D Nanometer Scale Raman PL Microspectrometer) 33 3-5-8動態光散射儀(Dynamic Light Scattering,DLS) 34 3-5-9介面電位量測儀(Zeta Potential Analyzer) 34 3-5-10黏滯係數測量儀(Viscometer) 34 3-5-11紫外光-可見光光譜儀(Ultraviolet–visible (UV/VIS) Spectophotometer) 34 第四章 結果與討論 36 4-1葡聚醣包覆之四氧化三鐵(Fe3O4)奈米粒子合成及官能基修飾 36 4-2 四氧化三鐵(Fe3O4)奈米粒子磁性量測 44 4-3 四氧化三鐵奈米粒子表面官能基鑑定 51 4-4 四氧化三鐵奈米粒子熱分析及其定量 58 4-5 四氧化三鐵奈米粒子X光繞射分析 69 4-6 四氧化三鐵奈米粒子拉曼光譜鑑定 755 4-7 四氧化三鐵奈米粒子DLS鑑定 78 4-8 四氧化三鐵奈米粒子Zeta potential及黏滯係數鑑定 85 4-9 TMZ包覆之四氧化三鐵奈米粒子鑑定 85 第五章 結論與未來工作 88 5-1 結論 91 參考文獻 92

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