Yu Qingsong, Zhang Jiajing, Zhang Guan, Gan Zhihua
State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029,, China.
Macromol Biosci. 2015 Apr;15(4):509-20. doi: 10.1002/mabi.201400416. Epub 2014 Dec 12.
Novel poly(ethylene glycol) and poly(N-(2-hydroxypropyl)methacrylamide) block copolymer (PEG-b-PHPMA) with well-defined composition was synthesized by RAFT polymerization. Folate and doxorubicin (DOX) were quantitatively introduced into the copolymer. The influences of folate content and pH value on folate receptor (FR) mediated cell endocytosis and pH-responsive DOX release were studied. It has been demonstrated that minimum folate content is needed for the enrichment of hydrophobic folate on the hydrophilic part of polymer conjugates. The cytotoxicity of targetable polymer drug conjugates was much higher than that of non-targetable ones and free DOX. It could be concluded that the folate plays a significant role in targeting and internalization of the conjugates against bladder cancer cells.
通过可逆加成-断裂链转移（RAFT）聚合反应合成了具有明确组成的新型聚乙二醇和聚（N-(2-羟丙基)甲基丙烯酰胺）嵌段共聚物（PEG-b-PHPMA）。将叶酸和阿霉素（DOX）定量引入到该共聚物中。研究了叶酸含量和pH值对叶酸受体（FR）介导的细胞内吞作用以及pH响应性阿霉素释放的影响。结果表明，在聚合物缀合物的亲水性部分富集疏水性叶酸需要最低的叶酸含量。靶向聚合物药物缀合物的细胞毒性远高于非靶向缀合物和游离阿霉素。可以得出结论，叶酸在缀合物对膀胱癌细胞的靶向和内化过程中起着重要作用。
