主-被动靶向细胞内还原引发释放的聚合物纳米胶束抗癌药物

发布时间：2018-02-26 21:56

  本文关键词： 主动靶向 还原敏感性 聚合物胶束 阿霉素 细胞毒性　出处：《西北师范大学学报(自然科学版)》2016年06期 　论文类型：期刊论文

【摘要】：先用开环聚合(ROP)合成大分子的RAFT试剂(PCL-SS-DMP),然后采用可逆加成-断裂链转移(RAFT)法,合成了亲水性的N-(2-羟丙基)甲基丙烯酰胺(HPMA)和主动靶向配体叶酸单体丙烯酰胺-叶酸(AA-FA),制备了具有主动靶向还原敏感性的两亲性嵌段共聚物(PCL-SS-b-PHPMA-b-PFA),用核磁共振(1 HNMR)对其结构进行表征.此共聚物在水溶液中可自组装形成聚合物胶束,由透射电子显微镜(TEM)和动态光散射(DLS)表征可知胶束为尺寸约100nm的球形颗粒,用DLS观察到胶束粒径在10mmol二硫苏糖醇作用下随时间的增加而逐渐增大.以抗癌药物阿霉素(DOX)为模型药物,研究载药胶束在模拟人体环境中的控释行为.用四氮唑盐还原法(MTT)研究不同浓度的聚合物胶束对人宫颈癌HeLa细胞的细胞毒性,并评价载药胶束在细胞中的抗癌效果.结果表明,PCL-SS-b-PHPMA-b-PFA可作为包载DOX的一种新型纳米材料,载药胶束的体外释放呈明显的还原依赖性,且具有较好的体外抗肿瘤活性,有望成为理想的抗肿瘤药物载体.
[Abstract]:The RAFT reagent, PCL-SS-DMPN, was synthesized by ring-opening polymerization (RP-ROP), and then the reversible addition-break chain transfer method (RATFT) was used. Amphiphilic block copolymers (PCL-SS-b-PHPMA-b-PFAA) with active targeting ligands, acrylamide / folate (AA-FAA) and active ligand folate monomers, were synthesized by the synthesis of hydrophilic N-PMA-2-hydroxypropyl) methacrylamide (HPMA-b-PFAA). The amphiphilic block copolymers with active targeting reduction sensitivity were prepared by 1HNMRs. The copolymer is self-assembled in aqueous solution to form polymer micelles. The micelles were characterized by TEM (TEM) and DLSs (dynamic light scattering). The micelles were spherical particles about 100nm in size. It was observed by DLS that the micelle particle size increased with the increase of time under the action of 10mmol / L disulfide. Dox, an anticancer drug, was used as the model drug. To study the controlled release behavior of drug-loaded micelles in simulated human environment, the cytotoxicity of different concentrations of polymer micelles to human cervical cancer HeLa cells was studied by tetrazolium reduction method. The results showed that PCL-SS-b-PHPMA-b-PFA could be used as a new nano-material for encapsulating DOX, and the release of drug-loaded micelles was obviously reductive in vitro and had good antitumor activity in vitro, the results showed that PCL-SS-b-PHPMA-b-PFA could be used as a novel nano-material for encapsulating DOX. It is expected to be an ideal antitumor drug carrier.
【作者单位】： 西北师范大学化学化工学院;
【分类号】：TQ317.5;;R945
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本文编号：1539832