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

癌症和心血管疾病是美国的主要死亡原因。了解如何设计纳米颗粒，直径为数十纳米的小颗粒，以有效地通过血液输送药物，将对下一代药物的开发产生巨大影响。 然而，很少有基于纳米颗粒的产品已经进入临床使用，因此对纳米颗粒的大小，形状和灵活性如何影响其生物学命运的基本理解是重要的。例如，一些研究表明，较长、较薄的颗粒显示出细胞摄取增强，而其他研究报告了相反的观察结果。因此，迫切需要对纳米颗粒如何在血流中运输以及它们的性质如何影响递送到其预期目标进行理论开发和实验。在这个研究项目中，不同性质的纳米颗粒正在实验室中生产，然后用于微米级通道的实验。 正在进行补充计算模型分析。这些结果为了解颗粒在血流中流动的行为、它们对血管壁的粘附以及它们被细胞吸收提供了重要的见解。一名博士后科学家、两名研究生、几名本科研究人员和高中生正在通过该项目接受培训。该研究项目旨在开发一种基于计算粒子的中尺度建模能力，用于预测尺寸，纵横比和灵活性如何影响纳米载体在血流中的运输以及随后对血管壁的粘附。这种计算工具能够预测纳米颗粒的生物学结果，并且在未来，可以帮助研究人员和制药公司为造影剂和药物递送载体等应用进行合理的纳米颗粒设计。该研究项目具有大量的实验组成部分，包括合成具有不同尺寸，纵横比和刚度的纳米颗粒库，以及在微流体直通道和分叉通道中测试其边缘和壁粘附力。从这项研究中获得的数据将影响跨学科的科学，包括数学建模，聚合物和纳米粒子化学以及纳米医学领域。

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.