Gold nanoparticles (AuNPs) are used in many applications; however, their interactions with cells and potential health risk(s) are not fully known. In this manuscript, we describe the interactions of AuNPs with human dermal fibroblasts and show that they can penetrate the plasma membrane and accumulate in large vacuoles. We also demonstrate that the uptake of the AuNPs is a function of time, their size and concentration. Specifically, we demonstrate that 45 nm AuNPs penetrate cells via clathrin-mediated endocytosis, while the smaller 13 nm enter mostly via phagocytosis. Furthermore, we provide evidence of cytoskeleton filament disruption as a result of AuNPs exposure and reconstitution during recovery (following AuNP removal), despite no changes in actin or beta-tubulin protein levels. In contrast, the expression of the extracellular matrix (ECM) proteins, collagen and fibronectin, was diminished in the cells exposed to AuNPs. We also examined the proliferation rates of cells exposed to AuNPs and show that its diminution is a function of apoptosis and speculate that apoptosis results from the number of vacuoles present in the cells, which is probably the main factor that disrupts the cytoskeleton causing cell area contraction and decreases in motility. Lastly, we also present data that indicates that AuNPs' damage to cells is not permanent and that the cells can completely recover as a function of AuNPs' size, concentration and exposure time. Taken together, our data suggest that AuNPs exert detrimental effects on cell function that could reverse following AuNPs removal.

Gold nanoparticles (AuNPs) are currently used in numerous medical applications. Herein, we describe their in vitro impact on human adipose-derived stromal cells (ADSCs) using 13 nm and 45 nm citrate-coated AuNPs. In their non-differentiated state, ADSCs were penetrated by the AuNPs and stored in vacuoles. The presence of the AuNPs in ADSCs resulted in increased population doubling times, decreased cell motility and cell-mediated collagen contraction. The degree to which the cells were impacted was a function of particle concentration, where the smaller particles required a sevenfold higher concentration to have the same effect as the larger ones. Furthermore, AuNPs reduced adipogenesis as measured by lipid droplet accumulation and adiponectin secretion. These effects correlated with transient increases in DLK1 and with relative reductions in fibronectin. Upon removal of exogenous AuNPs, cellular NP levels decreased and normal ADSC functions were restored. As adiponectin helps regulate energy metabolism, local fluctuations triggered by AuNPs can lead to systemic changes. Hence, careful choice of size, concentration and clinical application duration of AuNPs is warranted.

BackgroundTitanium dioxide (TiO2) is one of the most common nanoparticles found in industry ranging from food additives to energy generation. Approximately four million tons of TiO2 particles are produced worldwide each year with approximately 3000 tons being produced in nanoparticulate form, hence exposure to these particles is almost certain.ResultsEven though TiO2 is also used as an anti-bacterial agent in combination with UV, we have found that, in the absence of UV, exposure of HeLa cells to TiO2 nanoparticles significantly increased their risk of bacterial invasion. HeLa cells cultured with 0.1 mg/ml rutile and anatase TiO2 nanoparticles for 24 h prior to exposure to bacteria had 350 and 250 % respectively more bacteria per cell. The increase was attributed to bacterial polysaccharides absorption on TiO2 NPs, increased extracellular LDH, and changes in the mechanical response of the cell membrane. On the other hand, macrophages exposed to TiO2 particles ingested 40 % fewer bacteria, further increasing the risk of infection.ConclusionsIn combination, these two factors raise serious concerns regarding the impact of exposure to TiO2 nanoparticles on the ability of organisms to resist bacterial infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0184-y) contains supplementary material, which is available to authorized users.

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