新型高分子脂质体的多功能组装及对恶性脑瘤的治疗

项目名称： 新型高分子脂质体的多功能组装及对恶性脑瘤的治疗

项目编号： No.50873076

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 常津

作者单位： 天津大学

项目金额： 35万元

中文摘要： 本课题为克服脂质体做为药物载体存在的稳定性差缺陷，将自行合成的双亲性大分子十八烷基季铵盐接枝谷氨酸及其功能化衍生物替代磷脂，通过传统脂质体技术，制备得到具有跨血脑屏障功能、磁性和RGD靶向功能、体内长循环功能的高分子脂质体。以高分子脂质体技术为基础，同PLGA微球技术相结合，构建出多功能的核壳载体平台并用于基因/药物的共投递。研究结果表明，多功能PLGA/高分子脂质体载体粒径均一，尺寸可控，具有明显的核壳结构，同时具有优良的磁性能和药物缓释性能。细胞内吞实验和流式细胞仪的检测结果表明，核壳纳米载体能够成功地实现药物和基因的共投递，有效抑制肿瘤细胞的增值能力。动物实验结果表明，同时携带抗癌药物表阿霉素（EPI）和抗癌基因psi-EGFR质粒的磁性PLGA/多功能化高分子脂质体核壳结构载体在磁场作用下，对C6大鼠原位胶质瘤模型的药物和基因联合治疗效果明显优于单纯药物或基因治疗。本课题研究成果为最大程度的实现基因和药物对肿瘤的有效治疗提供了重要的科学依据。本项目在国内外杂志发表高水平SCI收录论文13篇，会议论文2篇；申请国家发明专利12项，其中授权2项。超额完成了预期目标。

中文关键词： 壳聚糖;高分子脂质体;磁性纳米粒子;PLGA;药物和基因投递系统

英文摘要： To overcome the disadvantages of conventional liposome, especially the unstability, the polymeric liposomes were synthesized from the octadecyl-quaternized lysine poly (γlutamic acid) (OQPGA) and its derivatives. Compared with conventional liposome, the polymeric liposome has multifunctions, such as crossing the blood brain barrier, targeting to the tumor tissue, long circulation time in vivo. Based on the formation technology of polymeric liposome, the PLGA/multifunctional polymeric liposome core-shell nanoparticles were prepared successfully and used as gene/drug co-delivery. The results showed that nanoparticles have core-shell structure with nanosize, sustained drug release profile and good DNA-binding ability. Importantly, the core-shell nanoparticles achieve the possibility of co-delivering drugs and genes to the same cells with high gene transfection and drug delivery efficiency. Besides, the anticancer therapy of co-delivering drugs and genes vectors is more effective than that of either drugs or genes in vivo experiment. All the results provided important experimental basis for the application of gene/drug co-delivery.

英文关键词： chitosan; polymeric liposome; magnetic nanoparticles; PLGA; drug and gene delivery system