An Integrated Biometric Platform for Evaluation of Nanomedicine Delivery

描述(申请人提供)：血管病理，如炎症、血栓、动脉粥样硬化和恶性肿瘤，需要准确定位成像和治疗剂以进行有效的诊断和治疗。该方案旨在开发一种新的仿生平台来评估载药纳米颗粒在血管床中的传输和生物分布。纳米颗粒的生物分布在很大程度上受局部血管几何形状和流动的影响。目前还没有简单的工具来预测复杂血管网络中的颗粒生物分布。这项工作的主要目标是通过补充微流体测试和计算建模来预测纳米药物在肺血管床中的传输和分布。这项拟议的研究将促进对纳米载体在血流中传输机制的了解，并将提供一个系统工具，以实现特定血管几何形状和血流动力学条件的靶向剂量和最佳分布。提出的工作目标是：(1)开发一个由基于血管形态的仿生微流控通道网络、靶受体和内皮涂层组成的微流控评价平台，用于确定纳米颗粒的结合分布和有效性；(2)应用多尺度模型模拟纳米颗粒在微流体通道和三维肺血管中的分布，并将模拟的分布与实验结果和现有的体内数据进行比较。与目前的流室和体内研究相比，该技术的主要优点是我们通过快速评估多参数和最小样本量，将药物纳米颗粒的分子结合与宏观生物分布联系起来。这种方法将能够准确和有效地估计纳米颗粒在患者特定血管几何形状中的生物分布。

DESCRIPTION (provided by applicant): Vascular pathologies such as inflammation, thromboses, atherosclerosis, and malignancies require accurate targeting of imaging and therapeutic agents for effective diagnosis and treatment. This proposal aims to develop a novel biomimetic platform to evaluate drug-carrying nanoparticle transport and biodistribution in a vascular bed. The nanoparticle biodistribution is largely influenced by local vascular geometry and flow. There is currently no simple tool to predict particle biodistribution in a complex vascular network. The primary goal of this work is to predict nanomedicine transport and distribution in a pulmonary vascular bed through complementary microfluidic tests and computational modeling. The proposed research will advance understanding of the mechanism of nanocarrier transport in the bloodstream, and will provide a systematic tool to achieve targeted dosage and optimal distribution for specific vascular geometries and hemodynamic conditions. The objectives of the proposed work are: (1) Develop a microfluidic evaluation platform consisting of a vascular morphology-based biomimetic microfluidic channel network, target receptor and endothelium coating for determination of nanoparticle binding distribution and efficacy; (2) Apply a multiscale model to simulate nanoparticle distribution in microfluidic channels and in a 3D lung vasculature, and compare the modeled distribution with experimental results and existing in vivo data. The major advantage of the proposed technique, compared to current flow-chamber and in vivo studies, is that we relate molecular binding of drug nanoparticles to macroscopic biodistribution using fast evaluation of multiple parameters and minimal sample volume. This methodology will enable accurate and efficient estimation of nanoparticle biodistribution in patient-specific vascular geometries.