Influence of shear stress and size on viability of endothelial cells exposed to gold nanoparticles

Abstract

Screening nanoparticle toxicity directly on cell culture can be a fast and cheap technique. Nevertheless, to obtain results in accordance with those observed in live animals, the conditions in which cells are cultivated should resemble the one encountered in live systems. Microfluidic devices offer the possibility to satisfy this requirement, in particular with endothelial cell lines, because they are capable to reproduce the flowing media and shear stress experienced by these cell lines in vivo. In this work, we exploit a microfluidic device to observe how human umbilical vein endothelial cells (HUVEC) viability changes when subject to a continuous flow of culture medium, in which spherical citrate-stabilized gold nanoparticles of different sizes and at varying doses are investigated. For comparison, the same experiments are also run in multiwells where the cells do not experience the shear stress induced by the flowing medium. We discuss the results considering the influence of mode of exposure and nanoparticle size (24 and 13 nm). We observed that gold nanoparticles show a lower toxicity under flow conditions with respect to static and the HUVEC viability decreases as the nanoparticle surface area per unit volume increases, regardless of size.Electronic supplementary materialThe online version of this article (10.1007/s11051-017-3993-5) contains supplementary material, which is available to authorized users.

Effect of Flow-Induced Shear Stress in Nanomaterial Uptake by Cells: Focus on Targeted Anti-Cancer Therapy

“…Ideally, nanomaterials, i.e., nanoparticles, or photothermal nano-agents should be tested on pre-clinical animal models of cancer therapy. However, using animal models is limited by ethical guidelines, also it is time and labor intensive [ 32 ]. To avoid the uncritical testing on animals, in-vitro and in-silico testing are used as preliminary evaluation due to their low cost, simplicity and better control on experimental conditions.…”

“…[ 66 ]. One more study was conducted by Fede et al to reveal the effect of FSS and size of spherical citrate stabilized gold nanoparticles on HUVEC [ 32 ]. They tested two batches of gold NPs (Batch 24 nm and Batch 13 nm).…”

“…They measured the NPs concentration in two methods, one based on the surface area per unit volume, while the other based on the number of NPs per unit volume. They found that the cells were less viable when the surface area was increased per unit volume irrespective of the NPs size [ 32 ]. Yazdimamaghani et al studied the effect of silica NPs density and flow conditions on cell cytotoxicity, uptake and sedimentation.…”

Integrating Biophysics in Toxicology

“…by intravenous injection, they are distributed in the circulation and via mediation of the vascular endothelium might enter adjacent tissues [117]. Fede et al described in two consecutive papers an increased resistance of HUVEC endothelial cells when exposed to gold nanoparticles (Au-NP) in presence of shear stress as compared to static conditions [106,108]. In more detail, after exposure of the cells to 13 ± 3 nm NPs, they observed decreased cytotoxicity and nanoparticle uptake when combined with flow stimulation (5 µL/min) in comparison to static incubation [106] and confirmed the results also with bigger particles (24 ± 8 nm) [108].…”

“…Fede et al described in two consecutive papers an increased resistance of HUVEC endothelial cells when exposed to gold nanoparticles (Au-NP) in presence of shear stress as compared to static conditions [106,108]. In more detail, after exposure of the cells to 13 ± 3 nm NPs, they observed decreased cytotoxicity and nanoparticle uptake when combined with flow stimulation (5 µL/min) in comparison to static incubation [106] and confirmed the results also with bigger particles (24 ± 8 nm) [108]. Similarly, reduced uptake of Au-NP in the same cell type was obtained following shear stress pre-conditioning (24 h pre-incubation, 10 dyne) and incubation under flow conditions [107].…”