本研究藉由原子轉移自由基聚合法( atom transfer radical polymerization, ATRP )成功合成出具有多重響應性之雙親性嵌段共聚高分子Azo-PCL-b-P(TEGMA-co-FA)以及Azo-PCL-b-P(TEGMA-co-TPE)，並使其於水溶液中自組裝形成混合微胞，作為奈米藥物載體，針對其環境響應性、螢光性質與釋放行為進行探討。
本研究以聚己內酯 ( poly(ε-caprolactone), PCL )作為疏水鏈段形成疏水核心，包覆疏水性藥物阿黴素( doxorubicin, DOX )，以triethylene glycol methyl ether methacrylate ( TEGMA )形成親水鏈段作為親水外殼主體，利用兼具缺氧響應及光響應性質之偶氮苯基團連接親水及疏水鏈段，並分別在高分子中引入葉酸單體與螢光基團四苯乙烯( triphenylethylene, TPE )，前者具有酸鹼響應性及主動標靶功能，後者則具有聚集誘導螢光性質。透過調整兩種高分子之組成比例，使混合微胞在酸性環境下的最低臨界溶解溫度( lower critical solution temperature, LCST )略高於正常體溫37 ℃，中性環境下則遠高於37 ℃，使其能在體內循環中非病灶區域維持良好穩定性，進入腫瘤細胞內的溶酶體後，由於酸性環境造成微胞崩解而釋放藥物，且因腫瘤環境的低氧情況導致生物還原酶過度表達，經由還原作用使偶氮鍵結斷裂導致微胞結構被破壞，促進藥物釋放，此外，於外部照射紫外光能使偶氮苯基團順反異構化，改變微胞內部結構而釋出藥物，提升藥物釋放的時空可控性。而TPE具有聚集誘導螢光性質，且其螢光光譜與DOX之吸收光譜高度重疊，可藉由螢光共振能量轉移( Förster Resonance Energy Transfer, FRET )現象來監測微觀藥物釋放行為。
藥物釋放結果顯示，此混合微胞於酸性環境下48小時的累積釋放量達80%，明顯高於中性環境( 30% )；照射紫外光後，酸性環境的累積釋放量提升至90%且釋放速率加快。而溶液的螢光光譜中，DOX與TPE之螢光面積比隨釋放時間下降，證實FRET效應隨細胞釋放後下降。細胞毒性測試證實空白載體具生物相容性，在缺氧環境下包覆藥物之混合微胞毒殺效果顯著高於一般環境，且主要經由主動標靶進入細胞。此研究成功整合多重響應機制與螢光性質，提升藥物釋放控制的精準度與釋放行為監測的即時性。

This study successfully synthesized a multi-responsive polymeric mixed micelle system using amphiphilic block copolymers, Azo-PCL-b-P(TEGMA-co-FA) and Azo-PCL-b-P(TEGMA-co-TPE), via atom transfer radical polymerization (ATRP) for the controlled delivery and real-time monitoring of the anticancer drug doxorubicin ( DOX ). These micelles feature a hydrophobic poly(ε-caprolactone) ( PCL ) core for drug encapsulation and a hydrophilic shell modified with folic acid ( FA ) for receptor-mediated active targeting. The carrier integrates multi-responsiveness, triggering drug release through pH-dependent phase changes that destabilize the micelle, hypoxia-induced cleavage of azobenzene bonds by overexpressed reductases, and UV-light photoisomerization. Furthermore, the inclusion of triphenylethylene ( TPE ), which exhibits aggregation-induced emission ( AIE ), enables real-time monitoring of drug release via Förster Resonance Energy Transfer ( FRET ); as DOX is released, the FRET effect decreases, allowing for the tracking of microscopic delivery behavior. Experimental results demonstrated that the system achieves up to 90% cumulative drug release under combined acidic and UV stimuli, and exhibits significantly higher toxicity to HeLa cells under hypoxic conditions compared to normoxia, proving its potential as a highly efficient and trackable nanomedicine platform.

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