EAGER: Understanding the flow dynamics and transport of nanoparticles in simulated tumor blood flows for improved cancer treatment

1250661 Ma纳米颗粒在将抗癌药物更特异性地递送至肿瘤方面显示出巨大的前景，从而减少对正常组织的毒副作用。纳米颗粒在肿瘤中的被动积累是由于增强的渗透性和保留（EPR）效应，这是由肿瘤脉管系统的渗漏性质和肿瘤中缺乏淋巴引流引起的。EPR效应是纳米药物载体成功的关键。该研究的目的是了解纳米颗粒在刺激血流中的流动动力学以及随之而来的EPR和边缘效应。为了实现这一目标，PI将构建新型微流体装置，模拟血液分叉和泄漏的肿瘤血管。然后将表征纳米颗粒在刺激的血流中的轨迹。探索包括流动的几何形状，颗粒大小，和悬浮介质流变学对颗粒边集的影响。这项拟议中的研究将加强我们对EPR效应的基本理解--EPR效应是抗癌药物被动靶向递送的标志。拟议研究的成功也将对纳米颗粒的合理设计产生深远的影响，以允许更特异性地将抗癌药物递送到肿瘤中，从而提高癌症治疗期间的患者舒适度并满足社会需求。

1250661MaNanoparticles show great promise in delivering anticancer drugs more specifically to tumors, thereby reducing the toxic side effects to normal tissues. The passive accumulation of nanoparticles in tumors is due to the enhanced permeability and retention (EPR) effect, caused by the leaky nature of the tumor vasculature and the lack of lymphatic drainage in tumors. The EPR effect is the key to the success of nanoparticle-based drug delivery. The objective of the proposed research is to understand the flow dynamics of nanoparticles in stimulated blood flows and the consequent EPR and margination effects. To achieve this objective, the PI will construct novel microfluidic devices that mimic blood bifurcation and leaky tumor blood vessels. The trajectory of nanoparticles in stimulated blood flows will then be characterized. Explorations include effects of flow geometry, particle size, and suspending medium rheology on particle margination. The proposed research will strengthen our fundamental understanding of the EPR effect - the hallmark of passive targeted delivery of anticancer drugs. The success of the proposed research will also have far-reaching implications on the rational design of nanoparticles to allow more specific delivery of anticancer drug into tumors, thereby increasing patient comfort during cancer treatment and fulfilling a societal need.