CAREER: Predicting Nanoparticle Targeted Delivery Efficacy in Vascular Environment through Multiscale Modeling

职业：通过多尺度建模预测血管环境中纳米颗粒的靶向递送功效

• 批准号: 1113040
• 负责人: Yaling Liu
• 金额: $ 40.37万
• 依托单位: Lehigh University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1113040&HistoricalAwards=false
• 关键词: CAREER; Predicting; Nanoparticle; Targeted; Delivery

0955214LiuNanoparticulate systems have been widely used in diagnostic imaging and targeted therapeutic applications in recent years. One of the major challenges in nanomedicine is to improve particle selectivity and adhesion efficiency under complex vascular flow conditions. To deliver nanomedicine directly to the desired diseased tissue while minimizing deposition/uptake by healthy tissues along the pathway, the design of nanoparticle need to be considered together with the diseased region's physical parameters (e.g. vascular diameter, blood flow rate, surface area, etc). The goal of the proposed career development strategy is to uncover the adhesion dynamics of nanoparticles and predict targeted delivery efficacy under complex vascular environment through a multiscale modeling approach. In pursue of this goal, a 3D multiscale model of nanoparticle transport, dispersion, and adhesion dynamics will be developed. Such model will be used to predict particle delivery efficacy in idealized vascular networks and vasculatures reconstructed from scanned images. A fully integrated multiscale model, linking different functional biological scales, imaging and physical system, will allow system level nanomedicine evaluation for the first time. The proposed multiscale simulation based method will provide a rigorous mathematical model of nanoparticle adhesion dynamics under complex vascular environment. Results of this work will pave the way toward new nanomedicine design and dosage choice guidances for targeted drug delivery. The proposed interdisciplinary research compliments the PI's educational goals by integrating research into educational and outreach activities such as graduate and undergraduate courses and engineering summer camps. An interactive website hosting graduate student's research projects will be created to allow high-school students to learn bio-nanotechnology online. The education plan will increase the awareness among high school teachers and students of the potential biomedical applications of nanotechnology, to advance understanding of nano-bio interfacial phenomena for students at all levels, and to increase minority participation in science and engineering.

近年来，刘纳米关节系统在诊断成像和靶向治疗应用中得到了广泛的应用。纳米医学的主要挑战之一是在复杂的血管流动条件下提高颗粒的选择性和黏附效率。为了将纳米药物直接输送到所需的病变组织，同时最大限度地减少沿途健康组织的沉积/摄取，纳米颗粒的设计需要与病变区域的物理参数(例如血管直径、血流速度、表面积等)一起考虑。提出的职业发展战略的目标是通过多尺度建模方法揭示纳米颗粒的黏附动力学，并预测复杂血管环境下的靶向递送效果。为了实现这一目标，将建立纳米颗粒传输、分散和附着动力学的三维多尺度模型。这样的模型将被用来预测理想的血管网络和从扫描图像重建的血管中的粒子输送效率。一个完全集成的多尺度模型，将不同的功能生物尺度、成像和物理系统联系起来，将首次允许进行系统级纳米医学评估。所提出的基于多尺度模拟的方法将为复杂血管环境下纳米粒子的黏附动力学提供一个严格的数学模型。这项工作的结果将为新的纳米药物设计和靶向给药的剂量选择指南铺平道路。拟议的跨学科研究通过将研究纳入教育和推广活动，如研究生和本科生课程以及工程学夏令营，补充了国际和平协会的教育目标。将创建一个托管研究生研究项目的互动网站，让高中生在网上学习生物纳米技术。该教育计划将提高高中教师和学生对纳米技术潜在生物医学应用的认识，增进各级学生对纳米生物界面现象的理解，并增加少数族裔对科学和工程的参与。