NANO-BLOOD: Modeling of BLOOD Flow and Vascular Wall Adhesion of Functionalized Non-Axisymmetric NANOcarriers

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Cancer and cardiovascular diseases are leading causes of death in the United States. Understanding how to design nanoparticles, small particles with diameters of tens of nanometers, to effectively deliver drugs through the blood stream would have a dramatic impact on the development of the next generation of pharmaceuticals. However, few nanoparticle-based products have advanced into clinical use, so a fundamental understanding of how the nanoparticle size, shape, and flexibility affect its biological fate is important. For example, some studies indicate that longer, thinner particles show enhanced uptake by cells, while other studies report the opposite observation. Therefore, there is a critical need for both theory development and experiments performed on how nanoparticles are transported in the blood stream and how their properties affect delivery to their intended target. In this research project, nanoparticles of varying properties are being produced in the laboratory and then used in experiments in micrometer-scale channels. Complementary computational modeling analysis is being performed. The results are providing important insights into the behavior of particles flowing in the blood stream, their adhesion to the walls of blood vessels, and their uptake by cells. A post-doctoral scientist, two graduate students, and several undergraduate researchers and high school students are being trained through this project. This research projects aims to develop a computational particle-based, mesoscale modeling capability for predicting how size, aspect ratio, and flexibility affect nanocarrier transport in the blood stream and subsequent adhesion to vascular walls. This computational tool enables the prediction of biological outcomes for nanoparticles and, in the future, may aid researchers and pharmaceutical companies with rational nanoparticle design for applications such as contrast agents and drug delivery vehicles. The research project has a substantial experimental component, including the synthesis of a library of nanoparticles with varying sizes, aspect ratios, and rigidities, and tests of their margination and wall adhesion in microfluidic straight and bifurcating channels. Data obtained from this research will impact science across scientific disciplines, including mathematical modeling, polymer and nanoparticle chemistry, and the field of nanomedicine.