Developing Targeted Therapeutic Nanosystems to Treat Metastatic Colon Cancer

开发靶向治疗纳米系统来治疗转移性结肠癌

基本信息

批准号：
9920182
负责人：
Martin Miguel Conda Sheridan
金额：
$ 27.91万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-01 至 2020-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9920182
关键词：
Affinity Antineoplastic Agents Apoptosis Atomic Force Microscopy Binding Biological Blood Circulation Cancer Model Cause of Death Cell Line Cell Survival Cells Cellular Assay Characteristics Charge Colon Colon Carcinoma Colonic Neoplasms Development Dissociation Dose Drug Delivery Systems Drug toxicity Encapsulated Epitopes Erythrocytes Fiber Fluorescence Fluorouracil Goals Hemolysis In Vitro Integral Membrane Protein Lesion Libraries Ligands Malignant Neoplasms Mass Spectrum Analysis Metastatic to Micelles Molecular Target Morphology Mus Nanosphere Nanostructures Nebraska Neoplasm Metastasis Normal Cell Normal tissue morphology Organ Peptides Performance Pharmaceutical Preparations Physiological Plasma Property Proteins Publishing Reporting Research Role Shapes Specificity Structure Surface Plasmon Resonance Surveys System Techniques Testing Therapeutic Agents Time Toxic effect Transmission Electron Microscopy Validation Water Woman base cancer cell claudin-1 protein computational chemistry computerized tools design effective therapy experimental study improved in silico in vivo light scattering men metastatic colorectal nanocarrier nanofiber nanosystems neoplastic cell novel novel therapeutics overexpression receptor binding receptor internalization targeted treatment zeta potential

项目摘要

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.

项目摘要/摘要：开发有针对性的治疗纳米系统来治疗转移性结肠癌这项研究的长期目标是建立一个纳米结构，该纳米结构可以针对结肠癌，包括其转移，同时提供治疗剂。在这个项目中，我们试图开发一个纳米系统可以靶向Claudin-1，这是一种在结肠癌及其转移中过表达的跨膜蛋白。这项目将检验以下假设：纤维样纳米结构可用于有效地靶向claudin-1。该项目由三个目标组成。第一个特定目的侧重于合成和表征可以在水中形成纳米结构的肽两亲物。多种纳米结构，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除其他方法。纳米结构库的毒性，结合亲和力和细胞内在化将评估含有claudin-1靶向肽的靶向肽。修改claudin-1的计算工具靶向肽将用于指导纳米结构靶向的优化。体内靶向然后将检查选定系统的功效。不同抗癌的封装效率纳米载体内的药物表现出最佳性能（基于毒性，稳定性和细胞绑定）将被评估。最后，封装在选定的药物的剂量依赖性毒性与单独游离药物相比，将评估针对结肠肿瘤细胞的纳米结构。