Flow Rate Affects Nanoparticle Uptake into Endothelial Cells

Nanoparticles are commonly administered through systemic injection, which exposes them to the dynamic environment of the bloodstream. Injected nanoparticles travel within the blood and experience a wide range of flow velocities that induce varying shear rates to the blood vessels. Endothelial cells line these vessels, and have been shown to uptake nanoparticles during circulation, but it is difficult to characterize the flow-dependence of this interaction in vivo. Here, a microfluidic system is developed to control the flow rates of nanoparticles as they interact with endothelial cells. Gold nanoparticle uptake into endothelial cells is quantified at varying flow rates, and it is found that increased flow rates lead to decreased nanoparticle uptake. Endothelial cells respond to increased flow shear with decreased ability to uptake the nanoparticles. If cells are sheared the same way, nanoparticle uptake decreases as their flow velocity increases. Modifying nanoparticle surfaces with endothelial-cell-binding ligands partially restores uptake to nonflow levels, suggesting that functionalizing nanoparticles to bind to endothelial cells enables nanoparticles to resist flow effects. In the future, this microfluidic system can be used to test other nanoparticle–endothelial cell interactions under flow. The results of these studies can guide the engineering of nanoparticles for in vivo medical applications.