【摘要】 该文合成了一种具有pH敏感性,较低毒性的两亲性嵌段共聚物以用于药物运输。聚乙二醇-聚己内酯(mPEG-PCL)是以聚乙二醇单甲醚为引发剂,开环己内酯聚合而成,阿霉素则是通过顺乌头酸裂解键连在聚己内酯的末端。该嵌段聚合物通过核磁共振、红外光谱等进行表征。共轭阿霉素后的嵌段聚合物在水溶液中能够自组装形成胶束,胶束粒径约为45.4 nm,透射电镜显示胶束具有近似的球形结构。阿霉素在pH=4.0下的释放速率明显快于pH=7.4下的释放速率。mPEG-PCL在细胞培养中无细胞毒性,包载阿霉素的胶束在人类MCF-7乳腺癌细胞上表现出迟缓的细胞毒性。通过共聚焦显微镜观察游离阿霉素和mPEG-PCL-DOX胶束在MCF-7细胞内的定位说明载体能够携带阿霉素进入细胞。更多还原

【Abstract】 The purpose of this experiment is to design and synthesize a pH-responsive amphiphilic block copolymer with low toxicity of the polymer micelles for drug delivery.Amphiphilic biodegradable diblock copolymer of poly(ε-caprolactone)(PCL)-monomethoxy poly(ethylene glycol)(mPEG) was synthesized by ring-opening polymerization of ε-caprolactone with mPEG as initiator.The doxorubicin was then attached to the PCL terminus via acid-cleavable cis-aconityl.The diblock copolymers were characterized by means of 1HNMR,FTIR,et al.Doxorubicin-conjugated mPEG-PCL diblock copolymers self-assembled to form micelles in aqueous solution,and the particle size determined by DLS was about 45.4 nm.TEM images show that these micelles were regularly spherical in shape.The release rate of DOX from the micelles at pH 4.0 was observed to be much faster than that at pH 7.4.The mPEG-PCL copolymer was nontoxic in cell culture,whereas DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells.The intracellular localization of free DOX,mPEG-PCL-DOX micelles in MCF-7 were observed by confocal laser scanning microscopy,showing that the carrier could take DOX into the cells.更多还原