本研究合成出三種雙親性嵌段高分子(amphiphilic block copolymer)：[PCL-b-P(TEGMA-co-AHA)]、[PCL-b-P(TEGMA-co-FA)]、[PCL-b-P(TEGMA-co-(PNA-HEMA))] ，此三種高分子在水溶液中可以自組裝形成高分子混合微胞，疏水核心為poly(ɛ-caprolactone) (PCL)可以包覆疏水性藥物(Doxorubicin, DOX)、親水外殼暨溫度響應為poly(triethylene glycol) (PTEG)，並修飾三種功能性單體：酸鹼響應6-aminohexanoic acid (AHA)、標靶功能folic acid (FA)和螢光影像單體4-pyrrolidine-1,8-naphthalimide (PNA)。
環境響應包括溫度(TEG)與酸鹼(AHA)雙重功能，藉由調整AHA在親水鏈段的比例調控高分子的LCST，中性環境LCST高於人體體溫37℃，酸性環境LCST低於37℃，因此在中性血液循環中可以穩定包覆藥物，進入癌細胞溶酶體酸性環境使微胞結構破壞釋放藥物；標靶功能是利用海拉細胞(Hela cell)表面具有過度表現的葉酸(Folic acid)受體，因此設計微胞帶有葉酸能主動標靶癌細胞並有效地在目標細胞快速累積；螢光影像使用嶄新的材料：4-pyrrolidine-1,8-naphthalimide (PNA)，其具有高強度螢光與細胞DNA嵌合等特性，而且其放射波長與藥物DOX吸收波長重疊，當兩者距離很近時會產生Förster Resonance Energy Transfer (FRET)，利用此特性可偵測微胞包覆與釋放藥物。
在in vitro 細胞毒性實驗顯示此高分子混合微胞不具有細胞毒性，包覆藥物的混合微胞能準確釋放藥物並毒殺癌細胞，證明此高分子混合微胞是極具潛力的藥物載體系統。

In this study, we developed a drug delivery system based on polymeric mixed micelles that co-assembled from three amphiphilic block copolymers, [PCL-b-P(TEGMA-co-AHA)], [PCL-b-P(TEGMA-co-FA)] and [PCL-b-P(TEGMA-co-(PNA-HEMA))]. The hydrophobic core is composed of poly(ɛ-caprolactone) (PCL) which can encapsulate hydrophobic drug (Doxorubicin, DOX), and poly(triethylene glycol) methacrylate (PTEGMA) is a thermo-sensitive polymer acted as hydrophilic shell of micelle. In addition, we introduced pH-sensitive (AHA), active targeting (FA) and fluorescent (PNA-HEMA) moieties to the hydrophilic block.
Our micelle has three functions：stimuli-sensitivity, active targeting and fluorescence image. “Stimuli-sensitivity” includes thermo- and pH- sensitive, we modulated the LCST of polymer higher than body temperature (37℃) at neutral pH and lower than 37℃ in acidic environment by adjusting the composition of AHA in hydrophilic block, therefore the mixed micelle steadily encapsulated drug in blood circulation at neutral pH and rapidly released drug in lysosome which is an acidic intracellular vesicle. Our micelle can “actively target” cancer cell by folic acid because Hela cells are overexpressed with folic acid receptors on the surface. “Fluorescence image” used brand new material：4-pyrrolidine-1,8-naphthalimide (PNA) which has high fluorescence intensity and good binding with DNA ability. In addition, FRET occurs when the spectral overlap and close proximity between PNA and DOX. We used FRET effect to detect our micelle encapsulated or released drug.
In vitro cytotoxicity suggested that polymer mixed micelle is nontoxic and drug-encapsulated mixed micelle has ability to kill cancer cells. These polymer mixed micelles are promising drug carrier for cancer therapy.

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