An Integrated Biometric Platform for Evaluation of Nanomedicine Delivery

描述（由申请人提供）：血管病变，如炎症、血栓形成、动脉粥样硬化和恶性肿瘤，需要成像和治疗剂的准确靶向，以进行有效的诊断和治疗。该提案旨在开发一种新型的仿生平台，以评估载药纳米颗粒在血管床中的转运和生物分布。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粒子在复杂血管网络中的生物分布。这项工作的主要目标是通过补充的微流体测试和计算建模来预测纳米药物在肺血管床中的运输和分布。拟议的研究将促进对血液中纳米载体运输机制的理解，并将提供一种系统的工具，以实现特定血管几何形状和血液动力学条件的目标剂量和最佳分布。本论文的主要目标是：（1）建立一个基于血管形态学的仿生微流控通道网络、靶向受体和内皮涂层组成的微流控评价平台，用于纳米粒子结合分布和功效的测定;（2）应用多尺度模型来模拟微流体通道和3D肺脉管系统中的纳米颗粒分布，并将模拟的分布与实验结果和现有的体内数据进行比较。所提出的技术的主要优点，目前的流动室和体内研究相比，是我们与药物纳米粒子的分子结合宏观生物分布使用多个参数和最小的样品体积的快速评估。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.