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

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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.