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

纳米血液：功能化非轴对称纳米载体的血流和血管壁粘附建模

基本信息

批准号：
1703919
负责人：
Joao Maia
金额：
$ 35.42万
依托单位：
Case Western Reserve University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2020-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1703919&HistoricalAwards=false
关键词：
NANO BLOOD Modeling Flow Vascular

项目摘要

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.

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，即直径数十纳米的小颗粒，以便通过血液有效地输送药物，将对下一代药物的发展产生重大影响。然而，很少有基于纳米颗粒的产品进入临床使用，因此从根本上了解纳米颗粒的大小、形状和灵活性如何影响其生物命运是重要的。例如，一些研究表明，较长、较细的颗粒显示出细胞摄取的增强，而另一些研究则报告了相反的观察结果。因此，迫切需要进行理论开发和实验，以了解纳米颗粒如何在血流中运输，以及它们的性质如何影响向预期目标的输送。在这项研究项目中，实验室正在生产不同性质的纳米颗粒，然后在微米级的通道中进行实验。正在进行互补性的计算建模分析。这些结果为了解血液中流动的颗粒的行为、它们与血管壁的粘连以及它们被细胞摄取提供了重要的见解。一名博士后科学家，两名研究生，以及几名本科生和高中生正在通过这个项目接受培训。本研究项目旨在开发一种基于粒子的计算中尺度建模能力，以预测尺寸、纵横比和灵活性如何影响纳米载体在血流中的传输以及随后与血管壁的黏附。这一计算工具能够预测纳米颗粒的生物结果，并在未来可能帮助研究人员和制药公司为造影剂和药物输送载体等应用进行合理的纳米颗粒设计。该研究项目有一个重要的实验部分，包括合成不同尺寸、长宽比和刚性的纳米粒子文库，以及测试它们在微流控直通道和分支通道中的边际和壁粘附性。从这项研究中获得的数据将影响跨科学学科的科学，包括数学建模、聚合物和纳米颗粒化学以及纳米医学领域。