CD基因修饰内皮祖细胞联合磁流体热疗靶向治疗肝癌的研究

项目名称： CD基因修饰内皮祖细胞联合磁流体热疗靶向治疗肝癌的研究

项目编号： No.81201131

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 陈蓉

作者单位： 东南大学

项目金额： 23万元

中文摘要： 肝癌位列我国恶性肿瘤死亡率的第2位，目前无特效疗法，自杀基因（CD）介导的生物治疗是潜在的有效手段，但缺乏肿瘤靶向性、对前体药物的给药时间尚需优化。利用纳米颗粒的超顺磁性进行的磁流体热疗具有高选择性和热均一性的优势，能增强其他治疗的效果，但其本身单一治疗效果有限。本项目拟：1、构建含自杀基因（CD）和荧光素酶基因（Luc）的重组慢病毒载体Lenti-CD/Luc-eGFP，将具有肿瘤靶向的人脐带血内皮祖细胞（EPCs）同时装载CD和Luc，体外标记超顺磁性氧化铁纳米粒子（SPIO），联合进行肝癌的基因治疗和磁流体热疗；2、综合利用磁共振和光学成像的各自优势，示踪移植细胞、监测热疗温度、指导CD基因治疗前药5-氟胞嘧啶（5-Fc）给予时间、评价治疗效果。本项目将可能为肝癌的治疗提供一种集肿瘤靶向追踪、联合生物治疗与热疗于一体的综合治疗策略，并为肿瘤治疗的疗效评价提供一种崭新的分子影像学手段。

中文关键词： 自杀基因；慢病毒；内皮祖细胞；磁共振；肝癌

英文摘要： The death rate of liver carcinoma ranks the 2nd of all cancers in China.To date, there are still no special stratagies for it's therapy. Suicide gene (Cytosine deaminase, CD) mediated biotherapy is a potential treatment method but lacks the specificity of tumor targeting, while the delivery time of prodrug needs to be optimized. With the advantage of high selectivity and thermal uniformity, magnetic fluid thermotherapy(MFH) can enhance therapeutic effect of other treatments. But it's own effect is limited.Our research will construct the recombinant lentivival vector Lenti-CD/Luc-eGFP containing cytosine deaminase(CD) gene and luciferase gene, arm human umbilical cord derived endothelial progenitor cells(EPCs) and label EPCs with superparamagetic iron oxide(SPIO) for liver carcinoma combining gene therapy and MFH. Associating the advantage of magnetic resonance imaging(MRI) and optics, we will trace the transplanting cells, instruct the administration of 5-Fc and evaluate the treatment effectiveness. This subject would offer a strategy for combining tumor targeted tracking, biotherapy associated with thermotherapy and evaluate the effectiveness for liver carcinoma and other malignant tumor.

英文关键词： Cytosine deaminase(CD)；Lentivirus；Endothelial Progenitor Cells(EPCs)；Magnetic resonance image(MRI)；Liver Carcinoma