砷化物抗肝癌活性及其免疫靶向载体的研究

项目名称： 砷化物抗肝癌活性及其免疫靶向载体的研究

项目编号： No.21201149

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 无机化学

项目作者： 宋晓丽

作者单位： 扬州大学

项目金额： 23万元

中文摘要： As2O3对肝癌有较好的治疗效果。三价单甲基及双甲基砷化物(MMAIII、DMAIII)是As2O3在肝脏中的代谢物，两者均能够引起DNA的直接损伤且损伤力远远大于As2O3,具有潜在的抗肝癌活性，此外砷化物毒性高，临床应用副作用较大。因此本项目将以人肝癌细胞SMMC-7721为细胞模型，系统研究比较As2O3、MMAIII、DMAIII的抗肝癌活性，并以生物相容性PEG-PLGA聚合物为载体材料制备载砷化物隐形纳米粒以降低其毒副作用；系统研究影响纳米粒包封率、载药量及控释速率的因素，筛选具有良好控释行为的载药粒子；通过纳米粒表面偶联抗肝癌单抗HAb18研制具有免疫靶向功能的砷化物纳米粒并研究其隐形功能及对肝癌细胞的作用；构建SMMC-7721小鼠肝癌模型并以此考察纳米粒靶向功能及抗肝癌活性以评价HAb18-PEG-PLGA载体的性能，为砷化物应用于肝癌的临床治疗提供理论基础和实践指导。

中文关键词： 砷化物；PLGA；控释；靶向；肝癌

英文摘要： Arsenic trioxide (As2O3) is effective for hepatoma treatment.Trivalent monomethylated arsenicals (MMAIII) and dimethylated arsenicals(DMAIII) are the metabolites of As2O3 in the liver, both of which can cause direct damage of DNA and the damage is far greater than As2O3.Thus, MMAIII and DMAIII have potential anti-hepatoma activity.In addition, arsenicals have high toxicity and are accompanied by high side effects in clinical applications. Thus in this project, we will first compare the effects of the trivalent methylated arsenicals and As2O3 to human hepatoma cell SMMC-7721 to evaluate their anti-hepatoma activities.Then we will synthesize the Biocompatibility PEG-PLGA polymer as the carrier material and prepare the arsenicals (As2O3, MMAIII, DMAIII)-loaded PEG-PLGA stealth nanoparticles to reduce the side effects of the arsenicals.The influence factors for encapsulation efficiency, drug load and the release rate will be systematically studied to select the nanoparticals with good controlled release behavior. Following that we will connect the anti-hepatoma monoclonal antibody HAb18 to the surface of the nanoparticals to prepare the immune targeting arsenicals-loaded nanoparticals, of which the stealth features and the effects to hepatoma cell will be investigated.Finally we will build the SMMC-7721 mouse hepat

英文关键词： Arsenic；PLGA；Controlled release；Target；Liver cancer