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研究生:潘世強
研究生(外文):Shih-Chiang Pan
論文名稱:具產氧性奈米複合物應用於光動力治療
論文名稱(外文):Oxygen-production Nanocomposites for Photodynamic Therapy
指導教授:賴秉杉
指導教授(外文):Ping-Shan Lai
口試委員:廖明淵謝銘鈞
口試委員(外文):Ming-Yuan LiaoMing-Jium Shieh
口試日期:2016-07-26
學位類別:碩士
校院名稱:國立中興大學
系所名稱:化學系所
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:62
中文關鍵詞:光動力治療腫瘤缺氧微脂體產氧粒子
外文關鍵詞:Photodynamic therapyTumor hypoxiaLiposomeOxygen-production particles
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光動力治療是近年來興起的一種癌症治療方法,藉由光敏劑轉化腫瘤環境中的氧氣以產生單態氧及活性氧物質來達到殺死腫瘤細胞的目的。然而腫瘤組織相較於一般組織是較為缺氧的環境且在光動力治療的過程中也會消耗組織環境中的氧氣,因此使得腫瘤深處嚴重缺乏氧氣,進而導致光動力治療的效率降低。
為了解決腫瘤缺氧的狀況,此研究是利用微脂體包覆的方法,將光敏劑、產氧粒子及氧化鐵奈米粒子包覆其中,製備出具產氧性的光敏性奈米複合物,如此一來就能增加光動力治療在腫瘤缺氧環境下的治療效率。此研究首先是合成了產氧粒子及氧化鐵的奈米粒子並鑑定其晶形結構,接著利用微脂體的方式與光敏劑進行包覆製備條件探討,藉由高解析穿透式電子顯微鏡的測定證實同時包覆此兩種奈米粒子。在生物特性測試部分,細胞存活率可明顯看出複合奈米粒子可提升光動力治療的效果。因此,所發展之產氧性光敏性奈米複合物對於腫瘤缺氧下的光動力治療效率上具有相當的潛力。


Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive oxygen species (ROS) or singlet oxygen (1O2) using photosensitizer plus light irradiation. However, pre-existing hypoxia in tumors and oxygen consumption during PDT results in an insufficient oxygen supply, thereby reducing therapeutic efficiency of PDT.
In this study, we demonstrated oxygen self-production photosensitive nanocomposites using liposomal photosensitizers plus oxygen-production particles and iron oxide nanoparticles (IONPs) to enhance PDT efficiency. Oxygen-production particles and IONPs were first synthesized and characterized and then co-loaded into liposome with photosensitizers. HR-TEM result showed that both nanoparticles were successfully loaded in one liposome. In biological test, oxygen level and PDT efficacy of photosensitizers was improved by oxygen-production liposome. Therefore, this photosensitive nanocomposites had the potential to enhance PDT efficiency in tumor hypoxia environment.


致謝辭 i
中文摘要 ii
Abstract iii
Table of contents iv
List of Figures vii
List of Tables x
Abbreviate table xi
Chapter 1 Introduction 1
1-1. Cancers 1
1-2. Photodynamic therapy 2
1-3. Tumor hypoxia 6
1-4. Oxygen carriers 9
1-5. Calcium peroxide 11
1-6. Fenton reactions 12
1-7. Nanocarriers and Liposomes 14
Chapter 2 Experimental design 17
Chapter 3 Materials and Methods 19
3-1. Materials 19
3-2. Synthesis of Calcium peroxide nanoparticles (CPONPs) 20
3-3. Synthesis of Iron oxide nanoparticles (IONPs) 20
3-4. Preparation of nanocomposites 21
3-5. Characteristics of nanocomposites 22
3-5-1. Element analysis and morphology identification 22
3-5-2. Encapsulation efficiency and drug loading 22
3-5-3. pH-sensitivity and stability 23
3-5-4. Measurement of singlet oxygen 23
3-6. In vitro studies 24
3-6-1. Cell culture 24
3-6-2. Cytotoxicity 24
3-6-3. Cellular uptake 25
3-6-4. Intracellular ROS 25
Chapter 4 Results and discussions 27
4-1. Characterizations of CPONPs 27
4-2. Characterizations of IONPs 33
4-3. Effect of preparation conditions of CPO/IO@Lip/Ce6 33
4-4. Characterizations of nanocomposites 38
4-4-1. Element analysis and morphology 38
4-4-2. Singlet oxygen-production efficiency and pH sensitivity 43
4-5. In vitro studies 44
4-5-1. Cellular uptake of the nanocomposites 44
4-5-2. Measurement of ROS production in normoxia and hypoxia environment 45
4-5-3. Cytotoxicity of nanocomposites in normoxia and hypoxia environment 51
Chapter 5 Conclusions 54
Reference 55


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