Investigation of nanoparticle extravasation pathways in tumor vessel-on-a-chip devices

The pathways through which nanomedicines extravasate from the bloodstream into solid tumors remain a subject of active investigation. To elucidate this process, we examine the predominant transport mechanisms in vitro using a tumor-vessel-on-chip (TVoC) microfluidic model device. The device comprises a micro-vessel lined with human umbilical vein endothelial cells, positioned adjacent to a compartment containing a collagen-based extracellular matrix. The two compartments are separated by a row of micropillars, where an endothelial barrier naturally forms at the interface within the gaps. Here, transport of different nanoparticles is analyzed under simulated vascular flow conditions. Strengthening endothelial cell junctions to modulate barrier properties led to a nearly 50 % reduction in the permeability coefficient. Furthermore, disruption of intracellular pathways resulted in minimal nanoparticle permeability, which is consistent with the interpretation that the tested nanoparticles predominantly extravasate via the interendothelial route.