Song Fei, Wang Zhidan, Gao Wenli, Fu Yu, Wu Qingrong, Liu Shouxin
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an, 710119, China.
Polymers (Basel). 2020 Oct 26;12(11):2482. doi: 10.3390/polym12112482.
Novel temperature/reduction dual stimulus-responsive triblock copolymers, poly [2-(2-methoxyethoxy) ethyl methacrylate--oligo (ethylene glycol) methacrylate]--(L-polylactic acid)-SS--(L-polylactic acid)--poly[2-(2-methoxyethoxy) ethyl methacrylate--oligo(ethylene glycol)methacrylate] [P(MEOMA--OEGMA)--PLLA-SS-PLLA--P(MEOMA--OEGMA)] (SPMO), were synthesized by ring opening polymerization (ROP) of L-lactide and 2,2'-dithio diethanol (SS-DOH), and random copolymerization of MEOMA and OEGMA monomers via atom transfer radical polymerization (ATRP) technology. The chemical structures and compositions of the novel copolymers were demonstrated by proton nuclear magnetic resonance (H NMR) and Fourier transform infrared spectroscopy (FTIR). The molecular weights of the novel copolymers were measured by size exclusive chromatography (SEC) and proved to have a relatively narrow molecular weight distribution coefficient (M ≤ 1.50). The water solubility and transmittance of the novel copolymers were tested via visual observation and UV-Vis spectroscopy, which proved the SPMO had a good hydrophilicity and suitable low critical solution temperature (LCST). The critical micelle concentration (CMC) of the novel polymeric micelles were determined using surface tension method and fluorescent probe technology. The particle size and morphology of the novel polymeric micelles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The sol-gel transition behavior of the novel copolymers was studied via vial flip experiments. Finally, the hydrophobic anticancer drug doxorubicin (DOX) was used to study the in vitro release behavior of the novel drug-loaded micelles. The results show that the novel polymeric micelles are expected to become a favorable drug carrier. In addition, they exhibit reductive responsiveness to the small molecule reducing agent dithiothreitol (DTT) and temperature responsiveness with temperature changes.
新型温度/还原双刺激响应性三嵌段共聚物聚[甲基丙烯酸2-(2-甲氧基乙氧基)乙酯-寡聚(乙二醇)甲基丙烯酸酯]-(L-聚乳酸)-二硫键-(L-聚乳酸)-聚[甲基丙烯酸2-(2-甲氧基乙氧基)乙酯-寡聚(乙二醇)甲基丙烯酸酯]P(MEOMA-OEGMA)-PLLA-SS-PLLA-P(MEOMA-OEGMA)，通过L-丙交酯和2,2'-二硫代二乙醇(SS-DOH)的开环聚合(ROP)，以及MEOMA和OEGMA单体通过原子转移自由基聚合(ATRP)技术的无规共聚反应合成。通过质子核磁共振(H NMR)和傅里叶变换红外光谱(FTIR)对新型共聚物的化学结构和组成进行了表征。通过尺寸排阻色谱(SEC)测量新型共聚物的分子量，结果表明其具有相对较窄的分子量分布系数(M≤1.50)。通过目视观察和紫外可见光谱对新型共聚物的水溶性和透光率进行了测试，结果表明SPMO具有良好的亲水性和合适的低临界溶液温度(LCST)。采用表面张力法和荧光探针技术测定了新型聚合物胶束的临界胶束浓度(CMC)。通过动态光散射(DLS)和透射电子显微镜(TEM)对新型聚合物胶束的粒径和形态进行了表征。通过小瓶翻转实验研究了新型共聚物的溶胶-凝胶转变行为。最后，使用疏水性抗癌药物阿霉素(DOX)研究了新型载药胶束的体外释放行为。结果表明，新型聚合物胶束有望成为一种良好的药物载体。此外，它们对小分子还原剂二硫苏糖醇(DTT)表现出还原响应性，并随温度变化表现出温度响应性。
