Developing Targeted Therapeutic Nanosystems to Treat Metastatic Colon Cancer

项目摘要/摘要：开发靶向治疗纳米系统来治疗转移性肿瘤 结肠癌 这项研究的长期目标是创造一种纳米结构，可以靶向结肠癌，包括其 转移，同时递送治疗剂。在这个项目中，我们试图开发一种纳米系统， 可以靶向Claudin-1，一种在结肠癌及其转移中过表达的跨膜蛋白。的 该项目将测试纤维状纳米结构可用于有效靶向Claudin-1的假设。 该项目包括三个目标。第一个具体目标集中在合成和表征 肽两亲物，可以在水中形成纳米结构。各种纳米结构、胶束和纤维， 将使用透射电子显微镜和原子力显微镜制备和表征 以及其他方法。纳米结构库的毒性、结合亲和力和细胞内化 将评估含有紧密连接蛋白-1靶向肽的细胞。用于修饰claudin-1的计算工具 靶向肽将用于指导纳米结构靶向的优化。体内靶向 然后，将对选定系统的功效进行检查。不同抗癌药物的包封率 纳米载体内的药物表现出最佳性能（基于毒性、稳定性和细胞毒性）， 将进行评估。最后，选择的药物包封的剂量依赖性毒性 与单独的游离药物相比，将评估纳米结构对结肠肿瘤细胞的作用。

Project Summary/Abstract: Developing Targeted Therapeutic Nanosystems to Treat Metastatic Colon Cancer The long-term goal of this research is to create a nanostructure that can target colon cancer including its metastases, while delivering a therapeutic agent. In this project, we seek to develop a nanosystem that can target Claudin-1, a transmembrane protein overexpressed in colon cancer and its metastases. The project will test the hypothesis that fiber-like nanostructures can be used to target Claudin-1 efficiently. The project consists of three aims. The first specific aim focuses on the synthesis and characterization of peptide amphiphiles that can form nanostructures in water. Diverse nanostructures, micelles and fibers, will be prepared and characterized using transmission electron microscopy and atomic force microscopy among other approaches. Toxicity, binding affinity and cell internalization of a library of nanostructures containing the Claudin-1 targeting peptide will be assessed. Computational tools to modify the claudin-1 targeting peptide will be used to guide optimization of nanostructure targeting. The in vivo targeting efficacy of selected systems will then be examined. The encapsulation efficiency of different anticancer drugs inside the nanocarriers that demonstrate the best performance (based on toxicity, stability and cell binding) will be assessed. Finally, the dose-dependent toxicity of drugs encapsulated in selected nanostructures against colon tumor cells will be evaluated in comparison to free drug alone.