用于抗肿瘤药物评价的三维肿瘤细胞体系的构建及性能  

3D Tumer Cell System for in Vitro Screening of Chemotherapeutic Drugs

作　　者：王雪琴[1] 曹丽华[1] 陈正坚[1] 罗军[1] 王红军[1,2] 涂克华[1,2] 蒋宏亮[1,2] 王利群[1,2] 

机构地区：[1]浙江大学高分子科学与工程学系 [2]教育部高分子合成与功能构造重点实验室,杭州310027

出　　处：《高分子学报》2014年第6期808-814,共7页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号21074112)资助项目

摘　　要：以聚己内酯和明胶为原料,通过静电纺丝制得孔隙率高、细胞分散性好、机械性能佳的三维细胞支架;扫描电镜及共聚焦显微镜表征U87细胞在该三维支架内培养14天后的生长情况,结果表明U87细胞不仅能够在支架表面黏附增殖,而且能迁移进入静电纺丝膜内部生长,形成良好的三维细胞体系.游离阿霉素(DOX)对二维表面和三维静电纺丝膜中U87细胞的细胞毒性结果表明,相对于二维细胞体系而言,三维细胞体系对药物的敏感性能降低.进一步比较了二维与三维细胞对负载于聚乙二醇-b-聚己内酯(PEG-b-PCL)胶束中DOX的响应,三维细胞体系的药物敏感性低于二维体系.Compared with 2D plate,3D tumor cell system is more like tumor tissue,for the 3D scaffold where cells grow can imitate the ECM in organisms, so that it could be used for evaluating anti-tumor efficacy of chemotherapeutic drugs with higher accuracy. There have been different ways to form a 3D scaffold, and electrospinning is the one with great potential. Although studies have shown that when exposed to drugs, greater amount of drugs are needed to kill the cells cultured on 3D scaffold,few studies have ever focused on the sensitive properties of 3D cell systems to drug delivery systems. As drug delivery system is going to be widely used in the future tumor treatment, in order to establish a drug delivery test model to predict the influence of drugs to tumor growth,a 3D cell culture scaffold composed of PCL and gelatin with high porosity,cell affinity and reasonable mechanical properties was fabricated through electrospinning method. One of the compositions PCL ensures the mechanical strength to avoid collapse and gelatin is a well known material with good biocompatibility. U87 was seeded on this scaffold,and the proliferation was monitored over 14 days with SEM and CLSM. It was found that U87 cells can not only adhere to the surface of the scaffold,but also migrate into the interior of the scaffold,forming a 3D cell system. When exposed to free DOX the electrospun scaffold was found to have lower drug sensitivity compared with the 2D cell culture plate. Further investigation of using Doxloaded PEG-b-PCL micelles as the delivery system demonstrated the same result.

关 键 词：电纺 三维细胞体系 阿霉素 胶束 

分 类 号：R730.5[医药卫生—肿瘤] TQ340.64[医药卫生—临床医学]