基于纳米锂皂石的药物输送体系用于乳腺癌的靶向化疗

利用纳米技术发展癌细胞靶向治疗的载体是当前纳米医学研究的热点和难点。本项目拟以具有良好药物负载和释放控制特性的纳米锂皂石(LAP)为基础载体，通过不同方式在其表面化学修饰靶向分子叶酸或单抗Herceptin，构建四种靶向纳米药物输送载体用于负载抗肿瘤药物阿霉素，评价锂皂石纳米颗粒表面修饰的树状大分子以及聚乙二醇对载体的药物装载效率、负载量和体外释放动力学的影响。通过体外细胞实验详细研究靶向修饰的载药纳米体系对乳腺癌细胞的靶向性和抑制效果，并通过人乳腺癌细胞小鼠动物模型考察载药纳米颗粒对乳腺癌的靶向治疗效果，为将来的临床试验提供坚实的理论和技术支持。项目首次提出将锂皂石纳米颗粒表面修饰靶向分子叶酸或单抗Herceptin，赋予载体对乳腺癌细胞的靶向功能，实现其在乳腺癌细胞表面的主动富集并特异性地将药物释放进入癌细胞，有望在乳腺癌的靶向治疗方面获得新突破。

Building efficient targeted drug delivery nanocarriers for cancer chemotherapy remains a major challenge in nanomedicine research. In this project, nano-sized laponite (LAP), a kind of nanomaterials with excellent drug-loading capacity and controlled release property, is proposed as basic vehicles, and then targeting agents, such as folic acid or antibody Herceptin, are modified on the surface of laponite by chemical reactions. Four different types of drug delivery nanoparticles loading anticancer drug doxorubicin will be synthesized using this strategy. The influence of modifying LAP surface with poly(ethylene glycol) and dendrimer on the drug loading, entrapment efficiency and drug release property will be evaluated. The targeting and inhibiting effect of synthesized targeted drug delivery nanoparticles on human breast cancer cells will be systemically studied in vitro. In addition, the in vivo targeted chemotherapy effects will also be investigated using nude mice tumor models, which may provide foundation and shed light on relevant technology for future clinic experiments. This project for the first time designs the modification of folic acid or antibody Herceptin on the surface of nano-sized laponite to enable active targeting to breast cancer cells. The designed nanocarriers are expected to actively target breast cancer cells and specifically release drug into cancer cells, which is very likely to lead to breakthrough in the targeted chemotherapy of breast cancer.