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

Study of Operando Characterization of Ferrocenyl Anti-Cancer Agents in Living Cell Using Surface-Enhanced Raman Scattering

蔡奇睿(Chi-Jui Tsai)

指導教授 ： 江建文

國立臺灣大學/理學院/化學研究所/碩士(2020年)

https://doi.org/10.6342/NTU202003266

摘要

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。

關鍵字

Ferrocifen ； 表面增強拉曼散射 ； 泰莫西芬 ； 感測

並列摘要

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.

並列關鍵字

Ferrocifen ； SERS ； Tamoxifen ； sensing

參考文獻

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