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研究生： Angela Fiona Patricia Sisnandy
Angela - Fiona Patricia Sisnandy
論文名稱： 利用藥物分子直接還原法製備藥物-奈米金共軛物以及其於癌症治療之應用
Synthesis of drug-gold nanoparticle conjugate using direct reduction by drug molecules for cancer therapeutics
指導教授： 戴 龑
Yian Tai
口試委員: 何明樺
Ming-Hua Ho
李振綱
Cheng-Kang Lee
張正琪
Cheng-Chi Chang
學位類別： 碩士
Master
系所名稱： 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年： 2013
畢業學年度： 101
語文別： 英文
論文頁數： 103
中文關鍵詞： 奈米金粒子 、無毒合成 、藥物輸送系統
外文關鍵詞： gold nanoparticles, green synthesis, drug delivery system
相關次數： 點閱：365  下載：9 
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  •  上一筆

    • 近年來無毒合成的奈米金粒子獲得了更多的關注尤其是在藥物輸送系統中，因為在生醫領域方面有很多廣泛的應用。在本研究中，我們用以化療藥物，5-FU和ALA還原劑和穩定劑並且用一步合成的方法來合成不同大小、型狀的奈米金粒子。
    我們初步利用可見光光譜儀、光致發光光譜儀、穿透式電子顯微鏡來鑑定奈米金粒子，此外，進一步利用可見光光譜儀進行定量的體外測試。接下來用表面增強拉曼光譜儀來證明奈米金粒子可以增強拉曼的訊號並且可以證明化療藥物與奈米金粒子之間的鍵結。更進一步用傅立葉轉換紅外光光譜儀、X光光電子能譜儀還有核磁共振譜
    對鍵結的分析。
    最後，體外和體內測試的結果顯示了5-FU和奈米金粒子之間的共振增加了一般細胞對癌症細胞的選擇率。我們對老鼠進行安全測試後發現，5-FU鍵結奈米金粒子可以降低AST和ALT的含量相較於沒有鍵結的5-FU；根據MTT測試，ALA鍵結奈米金粒子與沒有鍵結的ALA在受光激發前對於口腔癌症細胞前者毒性較強。

    關鍵字：奈米金粒子、無毒合成、藥物輸送系統

    Green synthesis of AuNPs was gained more interest due to wide application of AuNPs in biological field, especially in drug delivery system. In this research, a simple one step synthesis to produce AuNPs for bioapplication with various size and shape were reported by using chemotherapeutic drug, 5-FU and ALA as reducing and stabilizing agent.
    UV-Visible, PL and TEM were used as first characterization of AuNPs formed, in addition, UV-Visible also used for drug quantification in in vitro test. Surface enhanced raman spectroscopy (SERS) performed to proof that AuNPs can enhanced the raman signal of drug and also used to determine the bonding between chemotherapeutic drug and surface of AuNPs. Further binding characterization was conducted by FTIR, XPS and NMR.
    Finally, in vitro and in vivo results reveal that conjugation between 5-FU and AuNPs can increase its selectivity towards normal and cancer cells. Safety testing has been conducted and showed lower amount of AST and ALT for mice treated by 5-FU-AuNPs compared with mice treated by free 5-FU. MTT assay of ALA-AuNPs in oral cancer cells showed increasing cytotoxicity compared with free ALA even before light treatment.

    Keywords; gold nanoparticles, green synthesis, drug delivery system
    .

    ABSTRACT i 摘要 ii ACKNOWLEDGEMENTS iii CONTENTS iv LIST OF FIGURES vi LIST OF TABLES xi LIST OF ABBREVIATIONS xii CHAPTER I INTRODUCTION 1 CHAPTER II LITERATURE REVIEW 3 2.1. Gold Nanoparticle 3 2.1.1. Synthesis of Gold Nanoparticle 3 2.1.1.1. Citrate Reduction 3 2.1.1.2. The Brust-Schiffirin Method: Two-Phase Synthesis and Stabilization by Thiols 4 2.1.1.3. Seeding Growth 5 2.1.1.4. Shape Controlled Synthesis 6 2.1.1.5. Biosynthesis 7 2.2. Nanoparticle in Biomedical Application 10 2.2.1. Nanoparticle in Biosensing 11 2.2.1.1. Surface Plasmon Resonance (SPR) Properties 12 2.2.1.2. Fluorescence Properties 12 2.2.2. Nanoparticle in Drug Delivery 14 2.2.3. Nanoparticle in Photodynamic Therapy (PDT) and Photothermal Therapy 18 2.2.4. Cytotoxicity 20 2.3. 5-Fluorouracil (5-FU) 22 2.4. 5-Aminolevulinic Acid Hydrocloride (ALA) 24 2.5. Surface Enhanced Raman Scattering (SERS) 26 CHAPTER III EXPERIMENTAL 29 3.1. Materials 29 3.2. Equipments and Instruments 29 3.3. Experimental Procedure 30 3.3.1. Synthesis of AuNPs using 5-Fluorouracil 30 3.3.2. In vitro test of free 5-FU and 5-FU-AuNPs 31 3.3.3. In vivo test of free 5-FU and 5-FU-AuNPs 31 3.3.4. Synthesis of AuNPs using 5-Aminolevulinic Acid Hydrocloride 32 3.3.5. In vitro test of free ALA and ALA-AuNPs 33 3.4. Analytical Procedure 33 3.4.1. pH measurement 33 3.4.2. UV-Vis analysis 33 3.4.3. Photoluminescence analysis 33 3.4.4. Transmission Electron Microscopy analysis 33 3.4.5. Fourier Transform Infrared Spectroscopy analysis 33 3.4.6. Surface Enhanced Raman Spectroscopy analysis 34 3.4.7. X-Ray Photoelectron Spectroscopy analysis 34 3.4.8. Nuclear Magnetic Resonance analysis 34 CHAPTER IV RESULT AND DISCUSSION 35 4.1. Synthesis of 5-Fluorouracil conjugated AuNPs 35 4.1.1. Characterization 35 4.1.2. Effect of initial concentration of HAuCl4, pH and temperature 44 4.1.3. Quantification 51 4.1.4. In vitro and In vivo test 54 4.2. Synthesis of 5-Aminolevulinic acid hydrochloride (ALA) conjugated AuNP 62 4.2.1. Characterization 62 4.2.2. Effect of initial concentration, pH and temperature 73 4.2.3. In vitro test 84 CHAPTER V CONCLUSIONS AND FUTURE WORK 86 5.1 Conclusion 86 5.2. Future Work 87 REFERENCE 88

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