The influence of flow, shear stress and adhesion molecule targeting on gold nanoparticle uptake in human endothelial cells

The uptake of nanoparticles by endothelial cells is dependent on shear stress adaptation and flow exposure conditions. Adaptation of primary human umbilical vein endothelial cells (HUVECs) to shear stress for 24 h was associated with reduced internalisation of unmodified 80 nm spherical gold nanoparticles (AuNPs) (mean hydrodynamic size of 99 nm in culture medium) after exposure to flow conditions compared with cells that were cultured and exposed to static conditions. Under static conditions, targeting of 80 nm AuNPs conjugated with antibodies against the intracellular adhesion molecule 1 (ICAM-1) (mean hydrodynamic size of 109 nm in culture medium) markedly increased the internalisation of AuNPs in HUVECs that were activated with the tumour necrosis factor (TNF), a treatment that markedly increased the surface expression of ICAM-1. Shear stress-adapted and TNF-activated HUVECs, which were exposed to flow conditions, had higher association with anti-ICAM-1 AuNPs than cells that were not TNF-activated or exposed to particles under static conditions. Hence, shear stress adaptation reduces the uptake of unmodified AuNPs and increases the association between anti-ICAM-1 AuNPs and TNF-activated HUVECs.