本研究主要在製備具溫度及pH值雙重敏感性且具葉酸標靶的奈米複合載體以作為藥物控制釋放載體，利用腫瘤細胞上具有葉酸受體及腫瘤附近的pH值較低，希望藉由葉酸標靶的特性，使藥物載體在腫瘤細胞附近時，藥物載體表面上的葉酸與受體結合，再根據其酸鹼敏感的特性進行藥物釋放。此研究是利用丙烯酸(Acrylic acid, AA)與氮-異丙基丙烯醯胺(N-isopropylamide，NIPAAm)以可逆加成-斷裂鏈轉移聚合(Reversible addition-fragmentation chain transfer polymerization，RAFT)活性自由基聚合方法合成末端帶有酸基和十二烷基三硫代碳酸酯的窄分子量分佈PAA-b-PNIPAAm共聚物，作為環境敏感型高分子主體，並藉由調整高分子的pH值來控制低臨界溫度值(Lower critical solution temperature，LCST)，當pH值調整至6及7時，可以得到LCST接近於人體溫度37 oC，隨後透過動態光散射及TEM證明高分子具自組裝的能力。接著利用EDC/NHS活化葉酸上的酸基將其接枝至幾丁聚醣上，以紫外光-可見光分光光度計計算葉酸的接枝比，Chitosan-folate的葉酸接枝比為1.52%。最後，將PAA-b-PNIPAAm溶液加入葉酸修飾幾丁聚醣溶液中進行反應形成Chitosan-folate/PAA-b-PNIPAAm複合載體，以動態光散射探討其微胞型態。
In this study﹐dual thermo- and pH-responsive and folate-target nanocomposites were prepared to serve as potential carriers for controlled delivery of drugs. Reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylic acid (AA) and N-isopropylamide (NIPAAm) was used to synthesize PAA-b-PNIPAAm copolymers with acid and dodecyltrithiocarbonate end groups. The PAA-b-PNIPAAm copolymers were environment-responsive and had narrow molecular weight distribution. Adjusting the pH to 6 and 7 could bring the lower critical solution temperature (LCST) of the copolymers to around average normal body temperature (37 oC). Self-assembling properties of the copolymers were observed by dynamics light scattering (DLS) and transmission electron microscopy (TEM). Chitosan was modified with folic acid in HAc(aq)/DMSO through the reaction of amino group with carboxyl group. The degree of folic acid substitution was calculated to be 1.52%. At last, the Chitosan-folate/PAA-b-PNIPAAm composite carriers were prepared by adding the PAA-b-PNIPAAm solution into Chitosan-folate solution. DLS were used to investigate the micelle morphology of the Chitosan-folate/PAA-b-PNIPAAm composite carriers.