通用细胞膜粘接剂的合成与局部药物递送性能的测试

项目名称： 通用细胞膜粘接剂的合成与局部药物递送性能的测试

项目编号： No.21474103

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 于喜飞

作者单位： 中国科学院长春应用化学研究所

项目金额： 40万元

中文摘要： 药物载体系统是研究如何将有效治疗成分透过生物屏障，在指定的时间输送至靶细胞，并将药物的毒副作用降至最低，与发现新的治疗成分相比显得更为重要。多价胆碱磷酸（Choline Phosphate，CP）高分子材料可以快速粘接在具有磷脂结构的细胞膜表面（所有哺乳动物细胞），并且可以可被真核细胞快速内吞到细胞质内，因此可以作为药物载体材料应用到癌症等疾病的局部治疗领域。本项目以可聚合单体2-(Methacryloyloxy)ethyl Choline Phosphate（MCP）为细胞膜粘接剂的活性中心，聚合后得到多价CP高分子PMCP，通过’click’反应将聚乳酸接枝到PMCP的链端，制备嵌段共聚物PMCP-b-PLA，然后将PMCP-b-PLA制备亲水性胶束用于包裹紫杉醇，制备药物运载系统。通过体外细胞实验检测该药物运载系统的生物安全性，稳定性和治疗效果。

中文关键词： 药物输送；胆碱磷酸；加速细胞内在化；聚合物囊泡；

英文摘要： Eukaryotic cell consists of a nucleus, cytoplasm and cell membrane. The cell membrane is a biological membrane that separates the interior of all cells from the outside environment. It consists of the phospholipid (Phosphatidyl Choline lipids) bilayer with embedded proteins. Cell membranes are involved in a variety of cellular processes such as cell adhesion, ion conductivity and cell signalling and serve as the attachment surface for several extracellular structures, including the cell wall, glycocalyx, and intracellular cytoskeleton. However, what happens if we reverse the phosphate and choline? I didn't know but it rapidly became clear that nature did not make lipids or related species that contained the choline phosphate (CP) moiety; perhaps there was a reason that none had evolved although the structures of PC and CP ought to have similar properties unless they were oriented. As results of research, we found that simply reversing the order of the PC headgroup to CP produced a weak attraction between the two groups.The multivalent CP species could produce strong, controllable adhesion to any cell membrane containing PC-lipids, i.e. to any mammalian cell. The binding reaction can be reversed at some stage.We believe this is a new observation that will have many applications in the munipulation of biological s

英文关键词： drug delivery；choline phosphate；enhanced cellular internalization；polymersome；