Directed Transport Physics and Muli-Scale Therapy of Colon Cancer Liver Metatasis

结肠癌肝转移的定向传输物理和多尺度治疗

• 批准号: 8280458
• 负责人: MAURO FERRARI
• 金额: $ 86.16万
• 依托单位: METHODIST HOSPITAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8280458
• 关键词: Directed; Transport; Physics; Muli; Scale

PROJECT SUMMARY (See instructions): Liver metastasis is a common occurrence during the course of gastrointestinal disease. It has been found in 30-70% of patients who are dying of various malignancies including colorectal, breast, lung, and pancreas cancer. Surgery is a common therapy for liver metastasis; however, 5-year survival rates range from 25- 40%, indicating the need to develop novel therapies. A part of developing novel therapies is the necessity to understand the development of liver metastasis. Kupffer cells (KC), the phagocytic cells of the liver, comprise approximately 10% of all hepatic cells. The role of KC in liver metastasis is not cleariy understood; more specifically, it is not understood whether KC plays a defensive role against liver metastasis or enhances its angiogenesis. A better understanding of liver metastasis development and the role of KC is necessary to develop novel treatments for liver metastases. Another challenge in the treatment of cancers, including liver metastases, is the distribution of imaging and therapeutic agents to intended targets. Systemically administered drug molecules or contrast agents only reach their desired targets one part per 10,000-100,000. The overall goal of this project is to develop a broader understanding of physical barriers and biological factors involved in the progression of liver metastasis in orthotopic models of colorectal cancer and to design novel biocompatible delivery carriers able to overcome or take an advantage of these barriers with favorable pharmacokinetics and tissue distribution for highly efficient delivery of novel therapeutic agents and imaging agents. This project aims to image liver metastasis development and localization of KC in order to design an in silico model for administration of therapies and use a physical modeling process to optimize the properties of nanocarriers. Additionally, this project aims to refine, design, and evaluate biocompatibility of nanovectors for delivery of therapeutic and contrast agents for treatment of liver metastases, and to detennine therapeutic and imaging efficacy of co-delivery of gold nanoparticles and cytotoxic agents from rationally designed targeted multi-stage nanovectors in in-vivo models of liver metastases.

项目总结（见说明）： 肝转移是胃肠道疾病过程中常见的一种疾病。已经发现 30-70%的患者死于各种恶性肿瘤，包括结直肠、乳腺、肺和胰腺 癌手术是肝转移的常用治疗方法;然而，5年生存率范围为25- 30%。 40%，这表明需要开发新的治疗方法。开发新疗法的一部分是必要的， 了解肝转移的发展。枯否细胞（KC），肝脏的吞噬细胞， 约占所有肝细胞的10%。KC在肝转移中的作用尚不清楚; 更具体地说，尚不清楚KC是否对肝转移起防御作用， 增强血管生成。更好地了解肝转移的发展和KC的作用是 有必要开发新的治疗肝转移的方法。癌症治疗的另一个挑战， 包括肝转移，是成像剂和治疗剂向预定靶的分布。 全身给药的药物分子或造影剂只能达到其所需的目标，每 10,000-100,000.本项目的总体目标是对物理障碍有更广泛的了解 大肠癌原位模型中肝转移进展的生物学因素 并设计能够克服或利用这些屏障的新型生物相容性递送载体 具有良好的药代动力学和组织分布，用于高效递送新型治疗剂 试剂和显像剂。本项目旨在对KC的肝转移发展和定位进行成像 为了设计用于给予治疗的计算机模拟模型并使用物理建模过程 优化纳米载体的性质。此外，该项目旨在完善，设计和评估 用于递送治疗剂和造影剂的纳米载体的生物相容性 转移，并确定共递送金纳米颗粒和 来自合理设计的靶向多阶段纳米载体的细胞毒性剂在肝脏体内模型中的应用 转移