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標題: 評估光誘導顏色變化之螢光質做為生物感測器的可行性
Evaluation of photoinduced color changing fluorophore for a biosensor
作者: 林容至
Lin, Jung-Chih
關鍵字: 光動力治療
photodynamic therapy
photoinduced proton transfer
出版社: 生醫工程研究所
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摘要: 本研究中主要著重於對癌症的治療及檢測,實驗中我們利用3,6-bis[2-(1-methylpyridinium)vinyl]carbazole diiodide (BMVC)和porphyrin形成一個複合分子,成為光動力治療 (Photodynamic therapy, PDT)的二元系統,在系統中利用BMVC的螢光產生螢光共振能量轉移 (Fluorescence resonance energy transfer, FRET)至porphyrin,以提升porphyrin的PDT效果,並在PDT照光過程中發現細胞隨著照光產生螢光的變化,照光後細胞死亡並伴隨著細胞核逐漸產生亮綠色螢光,故在此二元系統中成功利用BMVC螢光產生FRET至porphyrin分子,光感物質porphyrin產生PDT殺死癌細胞,同時可做為一個細胞死亡的生物標記。鑑於細胞螢光變化的重要性,發現化合物2-(6-(4-aniline)-1,3-dioxo-1H-benzo[de]isoquinolin- 2(3H)-yl)-N,N-dimethylethanamine (ADA)於細胞內亦會照光產生細胞內螢光變化,除此之外觀察到ADA分子可利用螢光強度辨識正常細胞,期許ADA可做為標記正常細胞的螢光分子,在研究中發現ADA會產生激發態質子轉移的反應,以產生螢光光譜藍位移 (blue shift)並增強的變化,並且對於pH 具有敏感性,加酸後產生螢光下降,由於此特性,推測產生細胞內螢光強度不同的現象,為正常細胞與癌細胞中酸鹼度的差異性,此特性可應用在做癌症檢測時的控制組,預計算癌細胞於組織中的比例時,此螢光分子可作為計算中的分母,對於癌症檢測中提供醫生準確數字以達到更完善的癌症治療。
In this study, we focused on the therapy and diagnosis of cancers. Three binary molecule conjugates were designed and synthesized by conjugating a chromophore (3,6-bis-(1-methyl-4-vinylpyridinium)-carbazole diiodide, BMVC) to mono-, bis- and trishydroxyl photosensitizers, respectively. For this binary system, BMVC plays the role of cancer cells recognizer; fluorescence resonance energy transfer (FRET) donor to porphyrins, and also enhance the efficient of photodynamic therapy (PDT). In addition, the intracellular fluorescent colors switching upon photo-excitation are expected to be used for further cell death biomarker applications. Therefore the binary system was successful to apply the FRET effect to PDT, also killed the cancer cells selectively.Base on the study above, fluorescent color switching in cells is important for cancer cell recognization. Here, a pH-dependent fluorescence emission compound, 2-(6-(4-aniline)-1, 3-dioxo-1-H-benzo [de]isoquinolin -2(3H)-yl)-N,N-dimethyl-ethanamine (ADA), was designed and we investigated the excited state proton transfer (ESPT) behaviour when irradiation. The fluorescent intensity quenched once the compound ADA was protonated while irradiation resulted in emission blue-shift and intensity enhancement due to the ESPT. When cells were treated with ADA, the fluorescent intensity in normal cells is much higher than cancer cells due to their different degree of pH environment. On the other hand, intracellular fluorescent colors switching upon irradiatting. It hints that ADA is expected to become a normal cell biomarker as well as the control brackground in calculation the percentage of cancer cells in whole tissue.
其他識別: U0005-1608201220012800
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