本研究合成出具有聚集誘導螢光(AIE)性質之雙親性嵌段共聚高分子Thioketal-poly(-caprolactone)-b-poly(triethylene glycol methyl ether methacrylate -co-(1, 2, 3, 4, 5-pentaphenyl-1H-silol-1-yloxy) ethyl methacrylate)) (TKPCTAIE)以及具備多種環境響應性以及主動標靶特性之雙親性嵌段共聚高分子Thioketal-poly(-caprolactone)-b-poly(triethylene glycol methyl ether methacrylate-co-folic acid) (TKPCTFA)，將兩種高分子置於水溶液中自組裝形成高分子微胞，針對其螢光特性與環境響應性進行探討。
雙親性高分子之組成由疏水性鏈段poly(-caprolactone) (PCL)以及包含溫度響應性單體triethylene glycol methyl ether methacrylate (TEGMA)與具備酸鹼響應性與主動標靶特性之葉酸單體組成之親水性鏈段，因為在多數癌症細胞的表面都具有葉酸受體，因此在藥物載體表面修飾上葉酸作為配體後當受體與配體結合後即能夠順利進入至細胞內部，另外，因為葉酸本身具備的酸性，當其在生理環境內(pH 7.3)時，因為去質子化形成羧酸根離子使得水溶性提高，形成較為穩定之結構，反之當處於偏向酸性環境之腫瘤細胞內(pH 5.3)時，因為無法形成離子狀態導致溶解度下降，結構轉變為不穩定狀態。而親水性與疏水性鏈段之間則是以具有氧化還原響應性之縮硫酮(Thioketal)鍵結連接形成雙親性嵌段高分子TKPCTFA，另外再將螢光單體(1, 2, 3, 4, 5-pentaphenyl-1H-silol-1-yloxy) ethyl methacrylate (PPSHEMA)修飾於相似雙親性高分子之親水鏈段上，形成TKPCTAIE。
本研究藉由混合上述兩種高分子並且期望組成之高分子混合微胞之最低臨界溫度(LCST)於中性環境下高於人體體溫但在酸性環境下低於或接近於人體體溫，同時還可以藉由活性氧類物質(ROS)將縮硫酮鍵結切斷使得微胞型態崩解，因為在腫瘤細胞中會含有較高濃度之H2O2 (100 M)，而縮硫酮鍵結會與H2O2反應後段鍵形成硫醇，幫助釋放藥物以毒殺細胞。在本研究中包覆的藥物為阿黴素(Doxorubicin, DOX)，而螢光單體PPSHEMA之放射光譜與DOX之吸收光譜因為有部分重疊，所以當兩者距離足夠接近時(1~10 nm)便會發生Förster Resonance Energy Transfer (FRET)效應，可以藉由此現象判斷藥物釋放程度。
由藥物釋放的實驗結果可以證實本研究合成之高分子混合微胞在包覆藥物後於中性環境(pH 7.3)體溫(37℃)下兩天的釋放量約為15%，表示其在人體內運輸的過程中不會有大量的藥物洩漏，而隨著環境由中性變為酸性(pH 5.3)，藥物釋放量明顯上升，而加入ROS(100 M H2O2)後也可以提升藥物釋放量，最後當包覆藥物之混合微胞在酸性且含有ROS環境中釋放兩天可以達到接近70%的藥物釋放量，除此之外，透過細胞毒性實驗得知此包覆藥物之混合微胞IC50約為22 g/mL。

In this research, we synthesize two amphiphilic block copolymers, PCL-TK-b-P(TEGMA-co-PPPSHEMA) (TKPCTAIE) with aggregation induced emission (AIE) characteristic and PCL-TK-b-P(TEGMA-co-folic acid) (TKPCTFA) with multi-stimuli responsive and active targeting behaviors. Then we investigate a mixed polymeric micelle system self-assembled from these two copolymers. In this study, we focus on its fluorescent properties, environmental responsiveness, drug release, and cytotoxicity of HeLa cells of this mixed micelle.
In the micelle system, the hydrophobic chain of the polymer is made by poly(-caprolactone) (PCL) and the hydrophilic chain is made by TEGMA and folic acid. TEGMA is a thermos-responsive monomer and folic acid is a pH-responsive and active targeting monomer. Due to the variation of pH value among endosomes (pH 5.3), lysosomes (pH 5.3), and normal tissue (pH 7.3). Besides, the hydrophobic and hydrophilic chains are connected with thioketal, which is a redox-responsive bond. Furthermore, we connected the PPSHEMA with AIE characteristic to another amphiphilic block copolymer to form TKPCTAIE.
We controlled the lower critical solution temperature by changing the mixing ratio of TKPCTFA to TKPCTAIE. Moreover, we expect that higher reactive oxygen species (ROS) concentration (100 M H2O2) could cleave thioketal bond into acetone and thiol, and thus increasing the amount of drug release to kill tumor cells. The encapsulated drug in this research is doxorubicin (DOX). Because of the overlap of PPSHEMA fluorescent and DOX absorption spectrum, Förster Resonance Energy Transfer (FRET) would occur if PPSHEMA was closed enough to DOX. We could keep track of drug loading and drug release via FRET effect. Through the cytotoxicity test, we also prove the drug-loaded mixed micelles were the ability to kill the HeLa cells.

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