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研究生:曾千沛
研究生(外文):Chien-Pei Tseng
論文名稱:氧化鐵奈米粒子於體外三維培養淋巴內皮細胞及乳癌細胞之熱治療評估
論文名稱(外文):Hyperthermia Effect of Fe3O4 Nanoparticles on Three-Dimensional Growth of Lymphatic Endothelial and Breast Cancer Cells In Vitro
指導教授:林淑萍林淑萍引用關係
口試委員:賴秉杉陳宏基
口試日期:2016-07-12
學位類別:碩士
校院名稱:國立中興大學
系所名稱:生醫工程研究所
學門:工程學門
學類:生醫工程學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:56
中文關鍵詞:聚乙二醇二丙烯酸酯基底高分子支架Fe3O4磁性奈米粒子熱療SVEC4-10MCF-7
外文關鍵詞:Poly(ethylene glycol) diacrylate polymer scaffoldFe3O4 magnetite nanoparticleshyperthermiaSVEC4-10MCF-7
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淋巴轉移是最常見的轉移形式,並且也是腫瘤分期及治療乳癌患者的指標之一。在本項研究中選擇淋巴結內皮細胞(SVEC4-10)及人乳腺癌細胞(MCF-7),分別培養於體外三維高分子支架中,再加上Fe3O4磁性奈米粒子,觀察熱療效果對於細胞生長的情形。三維高分子支架由聚乙二醇丙烯酸酯基底高分子(PEGDA)前驅溶液,於可見光下光聚合而成,用於模擬真實生活環境。具光敏性PEGDA及聚乙二醇(PEG),以5:1形成三維高分子前驅溶液。為了控制溫度及熱療條件,不同濃度的Fe3O4磁性奈米粒子,包括50、80、100、150 ppm,分別加入PEGDA基底水膠中。將Fe3O4混合於PEGDA水膠中後,照射808 nm雷射光10分鐘,觀察其溫度變化,選擇適合的溫度於熱治療。將SVEC4-10及MCF-7細胞分別與含有80 ppm Fe3O4磁性奈米粒子的前驅溶液混合,進行於40.9 oC下熱療效果對細胞生長的影響 。SVEC4-10及MCF-7細胞分佈於三維培養環境中,分別培養1、3、5天後,進行rhodamine-phalloidin (紅色)及DAPI (藍色)螢光染色。結果顯示MCF-7細胞於42.9 oC的熱療條件下,培養5天後明顯下降。而SVEC4-10細胞於PEGDA基底水膠中,培養5天後,SVEC4-10細胞則正常生長。此外,三維高分子支架可以進一步利用於淋巴組織的再生。我們的結果顯示,Fe3O4磁性奈米粒子對於細胞具有生物相容性及適合建立熱療環境,能有效治療乳癌而不會損害淋巴生長。

Lymphatic metastasis is the most common form of metastasis and is one of the key factors in tumor staging and therapy in patients with breast cancer. In this study, lymphatic endothelial cells (SVEC4-10) and human breast cancer cells (MCF-7) were respectively cultured with polymer precursor solution containing Fe3O4 magnetic nanoparticles for in vitro observing the hyperthermia effect on cell growth. 3D polymer scaffold was synthesized by photopolymerization of poly(ethylene glycol) diacrylate (PEGDA)-based precursor solution under a visible light exposure for mimicking real living environment. Photosensitive PEGDA and poly(ethylene glycol) (PEG) were mixed at 5:1 ratio to form 3D polymer precursor solution. In order to control the temperature and the condition of hyperthermia, Fe3O4 magnetic nanoparticles with varied concentrations, including 50, 80, 100, 150 ppm, were added to PEGDA-based hydrogels, respectively. After that, Fe3O4 mixed PEGDA-based hydrogels were exposed under 808-nm laser light for 10 min, the changes of temperature were recorded in search of a suitable temperature used in hyperthermia treatment. SVEC4-10 and MCF-7 cells were respectively mixed in 80-ppm Fe3O4 precursor solution for the investigation of hyperthermia effect at 40.9 oC. The distribution of SVEC4-10 cells and MCF-7 cells in 3D culture environment was visualized by the fluorescent labeling of rhodamine–phalloidin (red) and DAPI (blue) on day 1, 3, 5 of culture. MCF-7 cells significantly decreased after 5 days of culture under hyperthermia condition at 42.9 oC. However, SVEC4-10 cells normally grew after 5 days of cell culture in PEGDA-based hydrogel. In addition, it is possible to consolidate 3D polymer scaffold to regenerate the lymphatic tissue. Our results showed Fe3O4 magnetic nanoparticles were biocompatible to cells and suitable to create a hyperthermia environment for effectively clinical treatment for breast cancer without damage of lymphatic endothelial growth.

第一章 緒論 1
1.1 前言 1
1.2 文獻回顧 1
1.2.1淋巴系統 1
1.2.2淋巴水腫 1
1.2.3乳癌的淋巴轉移 2
1.3 生醫材料之簡介 2
1.4 聚乙二醇基底高分子材料 3
1.5 熱療之簡介 4
1.5.1 熱療 4
1.5.2 光熱療治療法 5
1.6 磁性奈米粒子之簡介 6
1.6.1鐵磁性奈米粒子 6
1.6.2 磁性奈米粒子在生醫上的應用 6
1.7 研究動機與目的 6
第二章 材料與方法 8
2.1實驗材料 8
2.2實驗儀器 9
2.3實驗方法 10
2.4 PEG-PEGDA前驅溶液之製備 11
2.5 紅外線顯影系統 (Infrared Development System) 11
2.6 倒立式雷射共軛焦顯微鏡 (Laser Scanning Confocal Microscopy, LSCM) ……………………………………………………………………………..12
2.7 冷場發射掃描電子顯微鏡 (Field Emission Scanning Electron Microscope, FE-SEM) 12
2.8 細胞培養 13
2.8.1 細胞株 13
2.8.2 細胞培養基 13
2.8.3 細胞繼代 13
2.9 體外細胞生物相容性測試 (In vitro) 14
2.9.1 生物相容性測試 (DAPI & rhodamine-phalloidin) 14
第三章 實驗結果 15
3.1 PEGDA前驅溶液之合成 15
3.2 不同濃度Fe3O4磁性奈米粒子於PEGDA基底固態水膠之SEM及EDS分析 ……………………………………………………………………………..15
3.3 不同濃度Fe3O4磁性奈米粒子於PEGDA基底固態水膠之溫度變化 17
3.3.1 SVEC4-10及MCF-7細胞與Fe3O4磁性奈米粒子於PEGDA基底固態水膠之溫度變化……………………………………………………..19
3.4 SVEC4-10及MCF-7細胞於PEGDA基底固態水膠之螢光染色-Biocompatible Test(DAPI & Rhodamine-phalloidin) 21
3.4.1 SVEC4-10及MCF-7細胞於PEGDA基底固態水膠之螢光染色-控制組………………………………………………………………………. 22
3.4.2 SVEC4-10及MCF-7細胞於PEGDA基底固態水膠之螢光染色-照射808 nm雷射 26
3.4.3 SVEC4-10及MCF-7細胞於PEGDA基底固態水膠之螢光染色-添加Fe3O4奈米粒子 31

3.4.4 SVEC4-10及MCF-7細胞於PEGDA基底固態水膠之螢光染色-添加Fe3O4奈米粒子(80 ppm),照射808 nm雷射 36
3.4.5 SVEC4-10及MCF-7細胞於PEGDA基底固態水膠之螢光染色-添加Fe3O4奈米粒子(100 ppm),照射808 nm雷射 41
3.4.6 SVEC4-10及MCF-7細胞於PEGDA基底固態水膠之螢光染色-細胞核計數 45
3.4.7 SVEC4-10及MCF-7細胞於PEGDA基底固態水膠之細胞存活
率…………………………………………………………………………..47
第四章 討論 48
第五章 結論與未來展望 52
第六章 參考文獻 53
第七章 補充資料……………………………………………………………………56



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