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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 江建文(Kien Voon Kong) | |
dc.contributor.author | Chi-Jui Tsai | en |
dc.contributor.author | 蔡奇睿 | zh_TW |
dc.date.accessioned | 2021-06-16T09:48:08Z | - |
dc.date.available | 2020-08-21 | |
dc.date.copyright | 2020-08-21 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-15 | |
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C., Boto, A., Marín, R., Cury, D., Gómez, T., Fernández-Pérez, L., Lahoz, F., Díaz, M. Unique SERM-like properties of the novel fluorescent tamoxifen derivative FLTX1. Eur. J. Pharm. Biopharm. 85, 898-910 (2013). 16 Kong, K. V., Chew, W., Lim, L. H. K., Fan, W. Y. Leong, W. K. Bioimaging in the Mid-Infrared Using an Organometallic Carbonyl Tag. Bioconjugate Chem. 18, 1370-1374 (2007). 17 Kong, K. V., Lam, Z., Goh, W. D., Leong, W. K. Olivo, M. Metal Carbonyl–Gold Nanoparticle Conjugates for Live-Cell SERS Imaging. Angew. Chem. Int. Ed. 51, 9796-9799 (2012). 18 Policar, C., Waern J. B., Plamont, M.-A., Clède,S., Mayet, C., Prazeres, R., Ortega, J.-M. Vessières, A. Dazzi, A. Subcellular IR Imaging of a Metal–Carbonyl Moiety Using Photothermally Induced Resonance. Angew. Chem. Int. Ed. 50, 860-864 (2011). 19 Zrimsek, A. B., Chiang, N., Mattei, M., Zaleski, S., McAnally, M. O., Chapman, C. T., Henry, A.-I. Schatz, G. C. Van Duyne, R. P. 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SERS Imaging of Cell-Surface Biomolecules Metabolically Labeled with Bioorthogonal Raman Reporters. Chem. Asian J. 9, 2040-2044 (2014). 26 Vantasin, S., Ji, W., Tanaka, Y., Kitahama, Y., Wang, M., Wongravee, K., Gatemala, H., Ekgasit, S., Ozaki, Y. 3D SERS Imaging Using Chemically Synthesized Highly Symmetric Nanoporous Silver Microparticles. Angew. Chem. Int. Ed. 55, 8391-8395 (2016). 27 Fan, Z., Senapati, D., Khan, S. A., Singh, A. K., Hamme, A., Yust, B., Sardar, D., Ray, P. C. Popcorn-Shaped Magnetic Core–Plasmonic Shell Multifunctional Nanoparticles for the Targeted Magnetic Separation and Enrichment, Label-Free SERS Imaging, and Photothermal Destruction of Multidrug-Resistant Bacteria. Chem. Eur. J 19, 2839-2847 (2013). 28 Ando, J., Asanuma, M., Dodo,K., Yamakoshi, H., Kawata, S., Fujita, K., Sodeoka,M. Alkyne-Tag SERS Screening and Identification of Small-Molecule-Binding Sites in Protein. J. Am. Chem. 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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/59972 | - |
dc.description.abstract | Ferrocifen (Fe-Tam) 是二茂鐵為基底的抗癌藥劑,其對於癌症治療有顯著的臨床潛力。能夠直接偵測他們在活細胞中的中間產物,對於弄清他們的反增生效應是最重要的。反增生效應是對於設計更有效的化學治療藥物和化學策略,是避免特定的藥物抗性機制中標誌性的因子。這篇論文顯示了表面增強拉曼散射 (Surface-enhanced Raman scattering, SERS) 的威力,這是第一次直接偵測到二茂鐵基泰莫西芬 (ferrocenyl-based tamoxifen) 在活細胞中的氧化轉變過程。我們能夠觀察到ferrocenyl quinone methide (Fe-Tam-QM)在活細胞中明顯的振動特徵。理論計算也顯示了被觀察到的振動模式變化,是與二茂鐵相關的不同組態的振動模式。這些結果使我們能對二茂鐵為基底的藥物有更好的理解,能開發更多新穎的金屬衍生物的治療藥劑。 | zh_TW |
dc.description.abstract | Ferrocifen (Fe-Tam) is a ferrocenyl-based anti-cancer agent that holds significant clinical and translational potential in cancer therapy. Direct detection of their intermediates in living cells is of paramount importance to unravel their anti-proliferative action, a pivotal factor leading to designing more effective chemotherapy drugs and chemical strategies to circumvent specific drug resistance mechanisms. This study demonstrates, for the first time, the power of surface-enhanced Raman scattering (SERS) to directly detect oxidative transformation of ferrocenyl-based tamoxifen in living cell. Distinct vibrational features are observed for the formation of ferrocenyl quinone methide (Fe-Tam-QM) in a cell. Calculations show that the observed vibrational mode changes are resultant of the different configuration of ferrocenyl-related modes. These results provide a better understanding of the ferrocenyl-based medicine for developing more advanced metal-based therapy agents. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T09:48:08Z (GMT). No. of bitstreams: 1 U0001-1308202015205500.pdf: 3487214 bytes, checksum: b220d700df09c5ef975ac94dbf793e8b (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 目錄 摘要 ............................................................................................................................... I Abstract ....................................................................................................................... II 目錄 ............................................................................................................................ III 圖目錄 ...................................................................................................................... VV 表目錄 ......................................................................................................................... V 附圖目錄 ..................................................................................................................... V 第一章 引言 ................................................................................................................ 1 1-1 乳癌與泰莫西芬 ............................................................................................ 1 1-2 泰莫西芬衍生物的光譜偵測 ........................................................................ 2 1-3 表面增強拉曼散射 (Surface Enhance Raman Spectroscopy, SERS) ............. 3 1-4 研究動機 ....................................................................................................... 7 第二章 結果與討論 ..................................................................................................... 8 2-1 Fe-Tam的SERS光譜 .................................................................................... 8 2-2 監控Fe-Tam-QM與含硫醇基分子的反應 ................................................. 15 2-3 以奈米探針監控Fe-Tam-QM於細胞中的形成過程 ................................. 17 2-4 以奈米探針監控細胞週期的變化 ............................................................... 21 第三章 結論 .............................................................................................................. 24 第四章 實驗儀器與方法 ........................................................................................... 26 4-1 實驗藥品及溶劑 .......................................................................................... 26 4-2. 鐵泰莫西芬衍生物的製備 ......................................................................... 28 4-2-1 Fe-Tam-SM的製備-McMurry反應 ................................................ 28 4-2-2 Fe-Tam的製備-SN2反應................................................................ 29 4-3 拉曼光譜儀 (Raman micro-spectrometer) ................................................... 29 4-4 製造尖端含金奈米粒子、Fe-Tam的奈米探針 .......................................... 30 4-5 估計單一金奈米粒子上的Fe-Tam數量 .................................................... 31 4-6 偵測Fe-Tam以Ag2O的氧化及Fe-Tam-QM和硫醇分子的反應............. 32 4-7 以奈米探針做細胞內實驗 .......................................................................... 32 4-8 密度函數理論 (Density Function Theory, DFT) 計算................................ 33 第五章 參考資料 ...................................................................................................... 34 附圖 ............................................................................................................................ 38 圖目錄 圖1- 1 泰莫西芬及其衍生物之結構圖 ...................................................................... 1 圖1- 2 奈米溫度紅外光譜裝置示意圖、懸臂隨時間震盪的位移變化圖與所使用的羰基錸取代之二茂鐵泰莫西芬衍生物 ................................................................ 2 圖1- 3 金屬的LSPR示意圖 ...................................................................................... 3 圖1- 4 距離與SERS訊號強度關係圖 ....................................................................... 4 圖1- 5 Yang Tian團隊設計的SERS金奈米探針SEM顯示圖,能看到粗糙的金奈米附著在探針上 ................................................................................................... 5 圖1- 6 Yang Tian團隊所設計的SERS探針與其檢測示意圖 ................................... 6 圖1- 7 Yang Tian團隊所設計的SERS探針,在老鼠腦內測量其受ROS影響,CO32-濃度和pH值隨之變化調節的拉曼訊號圖譜和濃度變化圖............................... 6 圖2- 1 以氧化銀氧化Fe-Tam和Fe-Tam-QM與硫醇的反應之圖示 ....................... 8 圖2- 2 嵌入金奈米粒子的奈米探針SEM影像 ......................................................... 9 圖2- 3 探針的製備-於奈米探針末端修飾金奈米粒子............................................ 9 圖2- 4 探針於AFM 作用前後的SEM; 磨鈍前(a和d), 磨鈍後 (b和e) 連接金奈米粒子後 (c和f) ................................................................................................. 9 圖2- 5 探針在磨去惰性層時,過度磨損後的SEM圖像 ....................................... 10 圖2- 6 Fe-Tam粉末與Fe-Tam接在含金奈米粒子的探針上的拉曼光譜比較 ........ 10 圖2- 7 奈米探針浸泡於氧化銀和半胱胺酸溶液之圖示.......................................... 11 圖2- 8 Fe-Tam的實驗與理論計算SERS光譜 ......................................................... 12 圖2- 9 浸泡氧化銀後的Fe-Tam的實驗與理論計算SERS光譜 ............................ 13 圖2- 10 先浸泡於氧化銀再浸泡於半胱胺酸後的Fe-Tam的實驗與理論計算SERS光譜 .................................................................................................................... 14 圖2- 11 半胱胺酸與Fe-Tam-QM反應後,其2,575 cm-1的SH尖峰消失 ............ 15 圖2- 12 Fe-Tam 與不同硫醇分子反應後的SERS光譜 .......................................... 16 圖2- 13 當Fe-Tam-QM與不同的硫醇分子反應,902 cm-1尖峰消失的速率 ........ 16 圖2- 14 奈米探針與MDA-MB-231和 MCF-10A的細胞實驗,以及奈米探針穿透後的肌動蛋白螢光顯影 ..................................................................................... 17 圖2- 15 細胞外及細胞內的SERS光譜 ................................................................... 18 圖2- 16 奈米探針穿透MDA-MB-231細胞後的氧化壓力效應 (Mitotracker red染料)評估的實驗圖示............................................................................................ 19 圖2- 17 奈米探針在活的MDA-MB-231細胞中所得到的不同位置之SERS光譜 20 圖2- 18 奈米探針穿透細胞前後的明視野觀察及螢光顯影 .................................... 20 圖2- 19 以Mitotracker red染料測得的螢光強度 .................................................... 20 圖2- 20 奈米探針做MDA-MB-231的單一細胞實驗-細胞分裂中期 .................. 21 圖2- 21 奈米探針做MDA-MB-231的單一細胞實驗-細胞分裂末期 .................. 21 圖2- 22 細胞在不同週期測得的903 cm-1和1,105 cm-1尖峰的SERS 訊號強度 .. 22 圖2- 23 在奈米探針穿透進細胞後的實時掃描圖譜-MCF-10A ........................... 23 圖2- 23 在奈米探針穿透進細胞後的實時掃描圖譜-MDA-MB-231 .................... 23 VII 表目錄 表4- 1實驗所使用之藥品清單 ................................................................................. 26 附圖目錄 附圖 一 化合物Fe-Tam-SM之1H NMR圖譜 ....................................................... 39 附圖 二 化合物Fe-Tam-SM之1H NMR光譜圖-局部放大(0-3 ppm) ................. 40 附圖 三 化合物Fe-Tam-SM之1H NMR光譜圖-局部放大(3-4.5 ppm) .............. 41 附圖 四 化合物Fe-Tam-SM之1H NMR光譜圖-局部放大(6.5-8.5 ppm) ........... 42 附圖 五 化合物Fe-Tam之1H NMR光譜圖 .......................................................... 43 附圖 六 化合物Fe-Tam之1H NMR光譜圖-局部放大(2-3 ppm) ........................ 44 附圖 七 化合物Fe-Tam之1H NMR光譜圖-局部放大(3.5-4.5 ppm) .................. 45 附圖 八 化合物Fe-Tam之1H NMR光譜圖-局部放大(6.5-8.5 ppm) .................. 46 | |
dc.language.iso | zh-TW | |
dc.title | 以表面增強拉曼散射做活細胞中的二茂鐵抗癌藥劑之實時鑑定 | zh_TW |
dc.title | Study of Operando Characterization of Ferrocenyl Anti-Cancer Agents in Living Cell Using Surface-Enhanced Raman Scattering | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳振中(Jerry Chun Chung Chan),游景晴(Ching-Ching Yu) | |
dc.subject.keyword | Ferrocifen,表面增強拉曼散射,泰莫西芬,感測, | zh_TW |
dc.subject.keyword | Ferrocifen,SERS,Tamoxifen,sensing, | en |
dc.relation.page | 46 | |
dc.identifier.doi | 10.6342/NTU202003266 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-08-17 | |
dc.contributor.author-college | 理學院 | zh_TW |
dc.contributor.author-dept | 化學研究所 | zh_TW |
顯示於系所單位: | 化學系 |
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