本研究合成了三種不同功能的雙親性嵌段共聚高分子。第一種，合成了具有醛官能基單體的poly(ε-caprolactone)-SS-poly(Triethylene glycol methacrylate-co-4-formylphenyl methacrylate) (PCL-SS-b-P(TEGMA-co-PFMA))，並通過形成席夫鹼與阿黴素(DOX)結合，生成具有酸響應性的PCL-SS-b-P(TEGMA-co-DOX)。第二種，合成了poly(ε-caprolactone)-SS-poly(Triethylene glycol methacrylate-co-N-hydroxysuccinimide methacrylate) (PCL-SS-b-P(TEGMA-co-NSMA))，並將其改質後接上葉酸(folic acid)，形成具有多重環境響應性的高分子。第三種，包含螢光單體2-(1,2,3,4,5-pentaphenyl-1H-silol-yloxy) ethyl methacrylate (PPSHEMA)聚合，生成具有螢光性質的PCL-SS-b-P(TEGMA-co-PPSHEMA)。這些高分子在水溶液中以5:1:4的比例混合，自組裝形成具有三重刺激響應與螢光追蹤功能的高分子混合微胞系統，並針對其藥物釋放特性進行了詳細的檢測與探討。
這些雙親性高分子由疏水鏈段聚己內酯(PCL)和親水鏈段組成，親水鏈段包含具有溫度響應性的三乙二醇甲基丙烯酸酯(TEGMA)和具有反應官能基的甲基烯酸N-琥珀酸亞胺酯(NSMA)。NSMA經二乙胺取代成具有反應性的胺基，並與葉酸的γ-羧酸反應，形成具有酸鹼響應性與標靶性能的改質葉酸(FA)。此外，甲基丙烯酸4-甲醯基苯酯(PFMA)單體上的醛基與DOX上的胺基反應形成亞胺鍵，賦予其酸響應能力。具有聚集誘發螢光(AIE)性質的螢光單體PPSHEMA則賦予其螢光性質。
本研究通過調整聚合度和聚合物在混合微胞中的比例，使最低臨界溶液溫度(LCST)在酸性環境下達到36.4℃，略低於人體體溫(37℃)。此外，通過改變穀光甘肽(GSH)濃度，切斷雙硫鍵以釋放DOX，達到微胞崩解的效果。由於PPSHEMA的放射光譜與DOX的吸收光譜有足夠的重疊，當兩分子足夠接近時會發生螢光共振能量轉移(FRET)，本研究以FRET現象作為距離探針，觀察藥物載體的釋放情形。
實驗結果顯示，合成的混合微胞在中性環境下具有穩定性，且在體外釋放實驗中，於pH 5.3環境下能加速DOX釋放，達到57%，而在添加10 mM GSH的情況下釋放量增加至67%。在中性環境中，釋放量為25%，中性且加入GSH的組別釋放為37%。而此混合微胞經細胞毒殺實驗得知IC50約為20 μg/m，這些結果證明了本研究合成的混合微胞具有多重環境響應性和螢光追蹤功能，並且具有殺死癌細胞的能力。

In this study, three amphiphilic block copolymers were synthesized: PCL-SS-b-P(TEGMA-co-PFMA) with aldehyde groups, PCL-SS-b-P(TEGMA-co-FA) modified with folic acid, and PCL-SS-b-P(TEGMA-co-PPSHEMA) with fluorescent properties. These copolymers were mixed in a 5:1:4 ratio to form a polymer mixed micelle system with triple stimulus response and fluorescence tracking functions. The drug release characteristics were tested and discussed.
The amphiphilic polymers consist of a hydrophobic polycaprolactone (PCL) segment and a hydrophilic segment with temperature-responsive triethylene glycol methacrylate (TEGMA) and acid-base responsiveness. The aldehyde group on 4-formyl phenyl methacrylate (PFMA) reacts with the amine group on DOX to form an acid-responsive imine bond. The fluorescent monomer PPSHEMA provides aggregation-induced fluorescence (AIE) properties.
By adjusting the polymerization degree and polymer ratio, the lowest critical solution temperature (LCST) was set at 36.4°C in an acidic environment, slightly below human body temperature. Glutathione (GSH) concentration changes cleave the disulfide bond to release DOX, causing micelle disintegration. Fluorescence resonance energy transfer (FRET) was used as a distance probe to observe drug release.
In vitro release experiments showed that DOX release accelerated to 57% at pH 5.3 and increased to 67% with 10 mM GSH. In a neutral environment, the release was 25%, increasing to 37% with added GSH. The IC50 of the mixed micelle was approximately 20 μg/mL. These results demonstrate the mixed micelle's multiple environmental responsiveness, fluorescence tracking functions, and cancer cell-killing ability.

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