CRII: OAC: A Hybrid Finite Element and Molecular Dynamics Simulation Approach for Modeling Nanoparticle Transport in Human Vasculature

CRII：OAC：一种混合有限元和分子动力学模拟方法，用于模拟人体脉管系统中纳米颗粒的传输

• 批准号: 2326802
• 负责人: Ying Li
• 金额: $ 17.5万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2326802&HistoricalAwards=false
• 关键词: CRII; OAC; Hybrid; Finite; Element; CRII; OAC; Hybrid; Finite; Element

Through nanomedicine significant methods are emerging to deliver drug molecules directly to diseased areas for cancer treatment. Targeted drug delivery is one of the most promising approaches which relies on nanoparticles (NPs) that carry and release drugs. The therapeutic efficacy of NP-based drug carriers is determined by the proper concentration of drug molecules at the lesion site. NPs need to be delivered directly to the diseased tissues while minimizing their uptake by other tissues, thereby reducing the potential harm to healthy tissue. Therefore, the design of these NPs and hence the efficacy of the targeted drug delivery could be significantly improved by understanding how the drugs carried by NPs are transported and dispersed in human body. This project proposes a set of computational tools to model and investigate the transport and dispersion of NPs in human vasculature. This, in turn, can provide better imaging sensitivity, therapeutic efficacy and lower toxicity of NP-based drug carriers. The multidisciplinary nature of the project also brings together concepts from biology, engineering and computer science to educate the next generation of computational biologists, scientists and engineers. This research, thus, aligns with the NSF mission to promote the progress of science and to advance the national health, prosperity and welfare. The technical objective of this project is to create a hybrid finite element and molecular dynamics computational approach for modeling NP transport and adhesion in human vasculature. The realistic geometry of vascular network and fluid dynamics of blood flow are accurately captured through the finite element model. The microscopic interactions between NPs and red blood cells within blood flow and adhesion of NPs to vessel wall are resolved through the molecular dynamics simulation. A robust and efficient coupling interface is built to couple the finite element and molecular dynamics solvers. Specifically, this project aims to 1) create a multiscale and multiphysics computational model for predicting the vascular dynamics of NPs under the influence of realistic geometrical and physiochemical features of human vasculature; 2) craft an interface coupling technique that enhances computational accuracy and predictability by coupling the finite element and molecular dynamics solvers; 3) build testsuits for multiscale and multiphysics simulations for coupled solution error and convergence analysis; and 4) advance the current cyberinfrastructure to accelerate the material design process and enrich the cyber-enabled materials design community. Such a computational method can be used to explore how the vascular dynamics of NPs will be affected by their size, shape, surface and stiffness properties, as well as complex geometry of human vasculature. The simulation results can further guide experimentalists to design NP-mediated drug delivery platforms that optimally accumulate within diseased tissue to provide better imaging sensitivity, therapeutic efficacy and lower toxicity.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通过纳米医学，正在出现重要的方法，可以将药物分子直接传递到患病区域进行癌症治疗。 靶向药物输送是依赖携带和释放药物的纳米颗粒（NP）的最有前途的方法之一。 基于NP的药物载体的治疗功效取决于病变部位的药物分子的适当浓度。 需要将NP直接传递到患病的组织中，同时最大程度地减少其他组织的摄取，从而减少对健康组织的潜在危害。 因此，通过了解如何将NP携带的药物运输和分散在人体中，可以显着改善这些NP的设计以及靶向药物递送的功效。 该项目提出了一组计算工具，以建模和研究人类脉管系统中NP的运输和分散。 反过来，这可以提供更好的成像敏感性，治疗功效和基于NP的药物载体的较低毒性。 该项目的多学科性质还汇集了生物学，工程和计算机科学的概念，以教育下一代计算生物学家，科学家和工程师。因此，这项研究符合NSF的使命，旨在促进科学进步并促进民族健康，繁荣和福利。该项目的技术目标是创建一种混合有限元和分子动力学计算方法，以建模人类脉管系统中的NP传输和粘附。 血流的血管网络和流体动力学的现实几何形状通过有限元模型准确捕获。 通过分子动力学模拟，解决了血流中NPS与红细胞之间的微观相互作用，而NP与血管壁的粘附进行了分辨。 建立了强大而有效的耦合界面，以对有限元素和分子动力学求解器进行融合。 具体而言，该项目的目的是1）创建一个多尺度和多物理计算模型，用于预测NP的血管动力学，这是人类脉管系统的现实几何和生理化学特征的影响； 2）制作一种界面耦合技术，该技术通过耦合有限元和分子动力学求解器来增强计算精度和可预测性； 3）建立用于多尺度和多物理模拟的测试，用于耦合解决方案误差和收敛分析； 4）推进当前的网络基础设施，以加速材料设计过程并丰富网络支持的材料设计社区。 这种计算方法可用于探索NP的血管动力学如何受其大小，形状，表面和刚度特性以及人类脉管系统的复杂几何形状的影响。 模拟结果可以进一步指导实验者设计NP介导的药物输送平台，这些平台在患病组织中最佳地积累，以提供更好的成像敏感性，治疗功效和较低的毒性。该奖项反映了NSF的法定任务，并通过使用该基金会的智力功能和广泛的影响来评估Criteria，并通过评估来进行评估。