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

通过纳米医学，重要的方法正在出现，将药物分子直接输送到患病区域进行癌症治疗。 靶向给药是最有前途的方法之一，它依赖于携带和释放药物的纳米颗粒（NPs）。 基于NP的药物载体的治疗功效取决于药物分子在病变部位的适当浓度。 NP需要直接递送到患病组织，同时最大限度地减少其他组织对它们的吸收，从而减少对健康组织的潜在伤害。 因此，这些纳米颗粒的设计，从而靶向药物递送的功效可以显着提高通过了解纳米颗粒携带的药物是如何在人体内运输和分散。 本计画提出一套计算工具来模拟及研究奈米粒子在人体血管系统中的传输与分散。 这反过来可以提供基于NP的药物载体的更好的成像灵敏度、治疗功效和更低的毒性。 该项目的多学科性质还汇集了生物学，工程学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，以促进科学的进步和促进国家的健康，繁荣和福利。本项目的技术目标是建立一种混合有限元和分子动力学计算方法，用于模拟NP在人体血管系统中的转运和粘附。 通过有限元模型精确地捕捉血管网络的真实几何形状和血流的流体动力学。 通过分子动力学模拟，解决了纳米粒子与血流中红细胞之间的微观相互作用以及纳米粒子与血管壁的粘附。 一个强大的和有效的耦合接口，建立耦合有限元和分子动力学求解器。 具体而言，本项目的目标是：1）创建一个多尺度和多物理场计算模型，用于预测人体血管的真实几何和理化特征影响下的NP血管动力学; 2）制作一个接口耦合技术，通过耦合有限元和分子动力学求解器来提高计算精度和可预测性; 3）为多尺度和多物理场模拟建立测试服，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，丰富网络材料设计社区。 这种计算方法可以用于探索纳米颗粒的血管动力学将如何受到其尺寸、形状、表面和刚度特性以及人体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人员设计NP介导的药物递送平台，这些药物在病变组织内最佳地积聚，以提供更好的成像灵敏度、治疗效果和更低的毒性。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.