可靶、可控、可视复合纳米制剂的设计及介导肝癌综合治疗的机制研究

项目名称： 可靶、可控、可视复合纳米制剂的设计及介导肝癌综合治疗的机制研究

项目编号： No.31200750

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 张海军

作者单位： 东南大学

项目金额： 23万元

中文摘要： 肝癌严重威胁人类健康，尤我国为高发国之一，治疗效果尚不理想，提高疗效依赖于综合治疗。纳米复合物具有药物传输、诊断、治疗及疗效监测等多项功能，因此在肿瘤综合治疗领域具有广阔的应用前景。基于我们前期研究结果：纳米ZnO携载化疗药物联合化疗、光动力学治疗高效抑制肝癌细胞，丰富内涵、扩展外延，本项目将构建新型Fe3O4/ZnO纳米复合物装载阿霉素（DOX）及偶联转铁蛋白受体单克隆抗体的多功能制剂，探索肝癌综合治疗新策略。即有机结合纳米粒子被动靶向、抗体主动靶向及磁导靶向提高肿瘤靶向效能，进而利用制剂中DOX-ZnO载药方式呈现的pH 敏感性释药特性，实现在微酸性的肿瘤组织和细胞中智能选择性控释；体外研究制剂对肝癌细胞的DOX化疗、Fe3O4热疗、ZnO光动力学治疗及不同治疗方式组合的综合疗效和机制；应用肝癌动物模型，进行安全性、体内分布及磁共振可视化监测综合治疗疗效及机制研究，为临床应用提供依据。

中文关键词： 纳米复合物；综合治疗；肝癌；；

英文摘要： Hepatocelluar carcinoma seriously threatens human's health in the word, especially in our country. Improving outcome of the treatment depends on synthetic therapy since the current strategy has not always been suf?ciently effective. Nanocomposites with multifunction of drug delivery, diagnosis, therapy and monitoring treatment represent a promising opportunities for cancer synthetic therapy. Based on our previous study in which ZnO nanoparticles with anticancer drug mediated the combination modalites of chemotherapy and photodynamic therapy to induce the remarkable inhibition of hepatocarcinoma cells, we will fabricate the Fe3O4/ZnO nanocomposites loaded doxorubicin (DOX) and modified transferring receptor monoclonal antibody to explore the new strategy of synthetic therapy for hepatocelluar carcinoma. The nanocompisites could improve tumor targeting performance because of the integration of passive targeting, active targeting and magnetic targeting, and DOX could be intelligently released in the weak acid tumor site and tumor cells due to the pH-responsive structure DOX-ZnO. The relative in vitro anticancer activity and the mechanism of the nanocompisites mediated chemotherapy of DOX, hyperthermia of Fe3O4, and photodynamic therapy of ZnO as well as the different combinations of the single modality against hepa

英文关键词： Nanocomposites；Synthetic therapy；Hepatocelluar carcinoma；；