靶向肿瘤干细胞治疗肝癌的多模态影像研究

项目名称： 靶向肿瘤干细胞治疗肝癌的多模态影像研究

项目编号： No.81471632

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 许健

作者单位： 中国人民解放军东部战区总医院

项目金额： 70万元

中文摘要： 肿瘤干细胞(CSCs)是导致肝癌复发、转移的重要原因。CD133及EpCAM是其表面重要分子标记。研究发现表达CD133及EpCAM的肝癌干细胞具有强致瘤性及耐药性，导致肝癌治疗效果差。可以推测，肝癌干细胞表面CD133及EpCAM分子可以作为靶向治疗位点和疗效评价指标。本研究利用前期实验合成的多功能磁性介孔二氧化硅复合微球装载抗CD133和抗EpCAM的分子靶向药物及氟尿嘧定类化疗药物，并在其表面偶联抗CD133及EpCAM抗体，制成能特异性靶向CD133(+)EpCAM(+)CSCs的纳米药物治疗肝癌，同时采用多模态分子影像及磁共振功能成像技术监测疗效，最终以病理结果为参照标准，阐明特异性靶向CSCs的纳米药物在肝癌治疗中的作用和机制，检测CD133和EpCAM表达以评估肝癌疗效，探索靶向CD133(+)EpCAM(+)CSCs治疗肝癌的新方法及疗预后估新指标，达到提高肝癌疗效的目标。

中文关键词： 多模态；肿瘤干细胞；功能磁共振成像；靶向治疗；肝细胞肝癌

英文摘要： Cancer stem cells (CSCs) are the important cause of the recurrence and metastasis of hepatocellular carcinoma. CD133 and EpCAM are important molecular markers on its surface. The study found that the expression of CD133 and EpCAM liver cancer stem cells have a strong tumorigenicity and drug resistance, resulting in poor treatment of hepatocellular carcinoma. Presumably, the surface molecule CD133 and EpCAM of liver cancer stem cells can be used as targeted treatment sites and the indexes for evaluation. The research uses the synthesis of multifunctional magnetic mesoporous silica composite microspheres loading anti-CD133 and anti-EpCAM molecule targeted drugs and chemotherapy drug of fluorouracil, coupling of anti-CD133 and anti-EpCAM antibodies on it's surface, to make specific targeting CD133 (+) EpCAM (+) CSCs nano-drug for the treatment of hepatocellular carcinoma. While it uses multimodal molecular imaging and functional magnetic resonance imaging technology to monitoring the efficacy. In the final, the pathology results will be used as reference standard. It is to illustrate the effect and mechanism of the treatment of hepatocellular carcinoma by the specific targeting CSCs nano-drug，detect of the CD133 and EpCAM expression to assess the effect of hepatocellular carcinoma. It is to explore the new method for treatment of hepatocellular carcinoma by targeting CD133 (+) EpCAM (+) CSCs. The objective is to improve the curative effect of hepatocellular carcinoma.

英文关键词： multimodal;cancer stem cells;functional magenetic resonance imaging;targeted therapy;hepatocellular carcinoma