BACKGROUND: In general the prediction of the @entity137 and therapeutic efficacy of engineered nanoparticles in @entity1 is initially determined using in vitro static cell culture assays. However, such test systems may not be sufficient for testing nanoparticles intended for intravenous application. Once injected, these nanoparticles are caught up in the blood stream in vivo and are therefore in continuous movement. Physical forces such as shear stress and cyclic stretch caused by the pulsatile blood flow are known to change the phenotype of endothelial cells which line the luminal side of the vasculature and thus may be able to affect cell-nanoparticle interactions. METHODS: In this study we investigated the uptake of amorphous @entity3440 nanoparticles in primary endothelial cells (HUVEC) cultured under physiological cyclic stretch conditions (1 Hz, 5% stretch) and compared this to cells in a standard static cell culture system. The @entity137 of varying concentrations was assessed using cell viability and @entity137 studies. Nanoparticles were also characterized for the induction of an inflammatory response. Changes to cell morphology was evaluated in cells by examining actin and PECAM staining patterns and the amounts of nanoparticles taken up under the different culture conditions by evaluation of intracellular fluorescence. The expression profile of 26 stress-related was determined by microarray analysis. RESULTS: The results show that @entity137 to endothelial cells caused by @entity3440 nanoparticles is not significantly altered under stretch compared to static culture conditions. Nevertheless, cells cultured under stretch internalize fewer nanoparticles. The data indicate that the decrease of nanoparticle content in stretched cells was not due to the induction of cell stress, @entity32 processes or an enhanced exocytosis but rather a result of decreased endocytosis. CONCLUSIONS: In conclusion, this study shows that while the toxic impact of @entity3440 nanoparticles is not altered by stretch this dynamic model demonstrates altered cellular uptake of nanoparticles under physiologically relevant in vitro cell culture models. In particular for the development of nanoparticles for biomedical applications such improved in vitro cell culture models may play a pivotal role in the reduction of animal experiments and development costs.

In vitro investigation of XXXX nanoparticle uptake into @entity1 endothelial cells under physiological cyclic stretch.

@entity1 :: ('9606', 'Species') :: ['humans'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'cytotoxicity'] @entity3440 :: ('MESH:D012822', 'Chemical') :: ['silica']
@entity3440 :: (MESH:D012822,Chemical) :: ['silica']
