Fluid Flow Magnitude Impacts Nanoparticle Interactions with Endothelial Cells in Angiogenic Vessels

Nanoparticles, such as quantum dots (QDs), have to potential to deliver drugs to preselected targets within the body; dramatically improving their efficiency and efficacy. Differences in fluid flows result in phenotypic... [ view full abstract ]

Nanoparticles, such as quantum dots (QDs), have to potential to deliver drugs to preselected targets within the body; dramatically improving their efficiency and efficacy. Differences in fluid flows result in phenotypic changes and altered nanoparticle interactions in endothelial cells. Our work investigated the association of QDs with endothelial cells in various flow environments within angiogenic tissues. A zebrafish embryo model of angiogenesis was applied to investigate QD distribution in vivo, while a flow chamber provided controlled flow conditions in vitro.

Zebrafish embryos were injected with amino-terminated (N-) or carboxyl-terminated (C-) QDs at 52 hours post fertilization (hpf). QD distribution was analyzed by laser scanning confocal microscopy (LSCM) at time points ranging from 1 to 18 hours post injection (hpi). Human umbilical vein endothelial cells (HUVECs) exposed to fluid flow in a parallel plate flow chamber for 20 hours prior to QD exposure. Following 18 hour exposure, the HUVECs were fixed, stained and imaged by LSCM. Image analysis yielded quantified HUVEC-QD association data.

QDs associated with endothelial cells within the zebrafish embryos and, over time, were observed in the surrounding tissues. More QDs were found in the smaller blood vessels of the caudal venous plexus, with lower flow, than in the larger dorsal aorta. In vitro results support the in vivo observations with decreased QD association in HUVECs exposed to higher flow magnitudes. The significance of these findings on drug delivery remains uncertain, although heterogeneity in fluid flow may contribute to the limited tissue penetration of some nanoparticles.