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

1250661纳米微粒在将抗癌药物更具特异性地输送到肿瘤方面显示出巨大的前景，从而减少了对正常组织的毒副作用。纳米粒子在肿瘤中的被动积聚是由于肿瘤血管的渗漏性质和缺乏淋巴引流而引起的增强的通透性和滞留(EPR)效应。EPR效应是纳米粒给药成功的关键。这项研究的目的是了解纳米颗粒在刺激血流中的流动动力学，以及由此产生的EPR和边际效应。为了实现这一目标，PI将构建新的微流体设备，模拟血液分叉和泄漏的肿瘤血管。然后将描述纳米颗粒在刺激的血液流动中的轨迹。探讨了流动几何形状、颗粒大小和悬浮介质流变性对颗粒边际的影响。拟议的研究将加强我们对EPR效应的基本理解--被动靶向递送抗癌药物的标志。这项拟议研究的成功还将对纳米粒子的合理设计产生深远影响，使抗癌药物能够更具体地输送到肿瘤中，从而提高癌症治疗期间患者的舒适度，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.