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

• 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
• 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

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：开发靶向治疗转移瘤的纳米系统 结肠癌 这项研究的长期目标是创造一种能够靶向结肠癌的纳米结构，包括其 转移，同时输送一种治疗剂。在这个项目中，我们试图开发一种纳米系统 可以靶向Claudin-1，这是一种在结肠癌及其转移中过度表达的跨膜蛋白。这个 该项目将测试这样的假设，即纤维状纳米结构可以有效地靶向Claudin-1。 该项目由三个目标组成。第一个具体目标是合成和表征 可以在水中形成纳米结构的多肽两亲分子。不同的纳米结构、胶束和纤维， 将用透射电子显微镜和原子力显微镜来制备和表征 在其他方法中。纳米结构文库的毒性、结合亲和力和细胞内化 将对含有Claudin-1靶向多肽的药物进行评估。修改claudin-1的计算工具 靶向多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有效性。不同抗癌药物的包封率 纳米载体内的药物表现最佳(基于毒性、稳定性和细胞 约束性)将得到评估。最后，所选药物的剂量依赖毒性。 针对结肠肿瘤细胞的纳米结构将与单独使用的游离药物进行比较。