本研究針對具有三種環境響應性之雙親性嵌段共聚高分子Poly(ɛ-caprolactone)-SS-b-poly[triethylene glycol methacrylate-co- 6-(methacrylamido)hexanoic acid]於水中自組裝形成的高分子微胞進行奈米結構、環境應答、藥物包覆釋放及細胞毒性之探討與檢測。
雙親性嵌段共聚高分子以poly(ɛ-caprolactone) (PCL)為疏水性鏈段形成微胞內核、以具有溫度敏感性質之親水性單體triethylene glycol methacrylate (TEGMA)形成微胞外殼，內核可包覆疏水性藥物Doxorubicin (DOX)，外殼因其親水性於血液中有良好溶解度。在親水性鏈段上修飾酸鹼響應單體6-aminohexanoic acid (AHA)，親疏水鏈段之間以具有氧化還原響應性的雙硫鍵連接，使其具有特定環境響應之功能。
經由調整具酸鹼值響應單體AHA所占比例可以調整微胞的最低臨界溶解溫度(lower critical solution temperature, LCST)，使LCST於酸性環境低於體溫37℃，於中性環境下高於體溫37℃，分別對應癌細胞中溶酶體環境以及正常人體血液環境之酸鹼值，而雙硫鍵在高還原劑環境中，模擬腫瘤細胞質液之高濃度穀胱甘肽(Glutathione tripeptide, GSH)，發生斷鍵使微胞結構崩解，達到在血液中穩定包覆不釋放DOX，在腫瘤細胞中快速釋放藥物之目的。在細胞毒性實驗中，包覆藥物微胞對子宮頸癌細胞Hela cell有良好的毒殺效果，顯示雙親性嵌段共聚高分子微胞應用於疏水性藥物之載體，其奈米結構與環境響應之觸發釋放機制，是相當具有發展潛力的。

In this research, we investigated the nanosturctures, stimuli-responsive properties, drug encapsulation and release, and cytotoxicity to tumor cells of the triple stimuli-responsive polymeric micelles. The micelles were assembled of amphiphilic block copolymers, [PCL-SS-b-P(TEGMA-co-AHA)]. PCL is the hydrophobic core of micelle to encapsulate hydrophobic drug, Doxorubicin (DOX). PTEGMA is thermo-sensitive polymer as hydrophilic shell of micelle. The micelles were well-dispersed in aqueous solution because of the hydrophilic shell. In addition, we introduced pH-sensitive moieties (AHA) to the hydrophilic block. The connection between hydrophobic block and hydrophilic block is disulfide bond, which is redox-sensitive. Therefore, the micelles were stimuli-responsive.
　　By adjusting the composition of AHA and PTEGMA, the LCST of micelles is higher than body temperature (37℃) at neutral environment and lower than body temperature at acidic environment. Neutral and acidic environment simulated the condition in human circulatory system and in tumor cells, respectively. The disulfide bond is prone to rapid cleavage under a reductive environment through thiol–disulfide exchange reactions. Tumor tissues are highly reducing compared with normal tissues, with high concentrations of glutathione tripeptide (GSH). As a result, the drug-loading micelles were stable in the neutral and mildly oxidizing environment, which simulated circulatory system, and rapidly released drug in the acidic and highly reducing environment, which simulated tumor cells.
　　In the in vitro cytotoxicity test, Hela cancer cells were cultured with micelles. Blank micelles showed low toxicity, and drug-loading micelles successfully killed cancer cells. After a series of experiment, it showed that amphiphilic block copolymer is a promising material for controlled drug release.

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