Fig. 3.

Effect of microenvironmental cues on nanoparticle delivery. a An atherosclerosis model to assess the shear and inflammatory effects on membrane permeability. Membrane permeability increases with tumor necrosis factor alpha (TNF-ɑ) treatment and shear stresses, which results in increased nanoparticle translocation. Scale bar, 20 µm. b When PEGylated (PEG) and transferrin-functionalized (Tf) nanoparticles were flowed across a tumor-on-a-chip model (Fig. 2b), accumulation in tumor spheroid interstitial spaces doubled at a flow rate of 450 µl/h compared to a lower rate of 50 µl/h. c In the breast cancer tumor model (Fig. 2a), higher collagen concentrations did not affect nanoparticle translocation alone, but translocation increased under high collagen and cell packing. d A tumor-vasculature-on-a-chip platform was developed to model the effect of leaky vasculature near tumor sites. TNF-ɑ treatment increased intercellular gaps between endothelial cells (white arrows), mimicking leaky vasculature in vitro. Scale bars, 20 µm