本研究針對三組具特殊功能性官能基之雙親性嵌段共聚高分子Poly(ɛ-caprolactone)-b-poly[triethylene glycol methacrylate-co- 6-(methacrylamido)hexanoic acid] [PCL-b-P(TEGMA-co-AHA)]、Poly(ɛ-caprolactone)-b-poly[triethylene glycol methacrylate-co- N-(2-(methacrylamido)ethyl) folatic amide] [PCL-b-P(TEGMA-co-FA)]與Poly(ɛ-caprolactone)-b-poly[triethylene glycol methacrylate-co- (2-(1,2,3,4,5-pentaphenyl-1H-silol-1-yloxy)ethyl methacrylate)] [PCL-b-P(TEGMA-co-(PPS-HEMA))]於水中利用透析法形成的高分子混合微胞進行奈米結構、環境應答、標靶功能、細胞毒性以及生物螢光標記功能之探討與檢測。
以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TEGMA形成微胞外殼，內核可包覆疏水性藥物Doxorubicin(DOX)，外殼因親水性可具有較好溶解度於血液中，親水性鏈段TEGMA上另外接有酸鹼響應單體AHA、主動式標靶功能葉酸(FA)以及具螢光特性單體PPS-HEMA，使其具有特定功能。
經由調整具酸鹼值響應單體AHA所占比例以及各組雙親性嵌段高分子之比例可以調整混和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，達到在血液中穩定包覆不釋放DOX在癌細胞中迅速釋放藥物之目的。親水性鏈段修飾上葉酸(FA)可與癌細胞表面葉酸受體結合，使藥物具有主動式標靶功能，更加有效進入癌細胞內。PPS-HEMA單體具有AIE螢光性質，具有與藥物DOX重疊之吸收光譜，當兩者距離足夠接近即產生Föster Resonance Energy Transfer (FRET)現象，利用此現象可以作為判斷藥物是否包覆或是釋放的依據，也可以用來作為藥物載體之螢光標記，觀察是否進入癌細胞內。

In this research, we will investigated the nanosturctures ,stimuli-responsive ,fluorescence ,active targeting properties ,cytotoxicity for tumor cells and Bioimaging application of the multifunctional polymeric mixed micelles. The mixed micelles were co-assembled of three amphiphilic copolymers, [PCL-b-P(TEGMA-co-FA)], [PCL-b-P(TEGMA-co-AHA)] and [PCL-b-P(TEGMA-co-(PPS-HEMA))]. PCL is hydrophobic block as core of micelle to load hydrophobic drug, Doxorubicin (DOX). PTEGMA is thermo-sensitive polymer as hydrophilic shell of micelle to control the LCST of amphiphilic copolymers. In addition, we introduced pH-sensitive (AHA), active targeting (FA) and fluorescent (PPS-HEMA) moieties to hydrophilic block by copolymerization of these monomers with TEGMA, respectively. With control the composition of AHA and PTEGMA, the LCST of mixed micelles is higher than body temperature (37℃) at neutral environment but lower than body temperature at acidic environment. Folic acid (FA) can be combined with folic acid receptor on the surface of cancer cells, so that the drug has active target function, more effective into the cancer cells. The FRET from PPS-HEMA moieties to Doxorubicin encapsulated in the micelle was observed that indicated a successful encapsulation of drug in the core of polymeric micelles. FRET phenomenon can be used as a basis for judging whether the drug is encapsulated or released and can also be used as a fluorescent marker for the drug carrier to see if it enters cancer cells by Endocytosis.
Keyword: amphiphilic block copolymer, thermo-responsive polymer, pH-responsive polymer, aggregation-induced emission, folic acid, active target, bioimaging

文獻回顧

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