Liang Xing, Liu Fei, Kozlovskaya Veronika, Palchak Zachary, Kharlampieva Eugenia
Department of Chemistry and §Center for Nanoscale Materials and Biointegration, University of Alabama at Birmingham, Birmingham, Alabama, 35294, United States.
Department of Chemistry and Center for Nanoscale Materials and Biointegration, University of Alabama at Birmingham, Birmingham, Alabama, 35294, United States.
ACS Macro Lett. 2015 Mar 17;4(3):308-311. doi: 10.1021/mz500832a. Epub 2015 Feb 20.
We present synthesis and assembly of novel thermoresponsive block copolymers with double LCST precisely controlled within the physiological temperature range. Two separate phase transition temperatures were achieved by RAFT polymerization of structurally similar monomers with varied hydrophobicity. The LCST1 was varied from 19 to 27 °C by copolymerization of -vinylcaprolactam with a novel hydrophobic monomer, 3-methyl--vinylcaprolactam, while the LCST2 at 41-42 °C was attained by copolymerization of -vinylcaprolactam with hydrophilic -vinylpyrrolidone. The LCST1 facilitates micelle formation and entrapment of anticancer drug doxorubicin or hydrophobic dye Nile Red into the micelle core surrounded with hydrophilic yet temperature-sensitive corona. The LCST2 induces collapse of the micelle corona and the consequent drug release. The second elevated temperature is typical for tumors and can trigger the drug-loaded micelle aggregation/accumulation within the tumor resulting in the enhanced passive targeting.
我们展示了新型热响应性嵌段共聚物的合成与组装，其双低临界溶液温度在生理温度范围内得到精确控制。通过对具有不同疏水性的结构相似单体进行可逆加成-断裂链转移（RAFT）聚合，实现了两个不同的相转变温度。通过将N-乙烯基己内酰胺与新型疏水性单体3-甲基-N-乙烯基己内酰胺共聚，低临界溶液温度1（LCST1）在19至27°C之间变化，而通过将N-乙烯基己内酰胺与亲水性N-乙烯基吡咯烷酮共聚，在41 - 42°C获得低临界溶液温度2（LCST2）。LCST1促进胶束形成，并将抗癌药物阿霉素或疏水性染料尼罗红包裹在由亲水性但对温度敏感的冠层包围的胶束核心中。LCST2诱导胶束冠层塌陷并随之释放药物。第二个升高的温度是肿瘤所特有的，可引发载药胶束在肿瘤内聚集/积累，从而增强被动靶向性。
