However, human exposure is not new and AgNPs have a history of more than 100 years of use. Inevitably, from the rapid increase in its manufacture and utilization follows an increased human exposure, whereas the potential toxicity has yet to be fully addressed. The in vitro toxicity of AgNPs has been evaluated selleck chem Gefitinib in a wide range of studies but there is still a lack of consistent and reliable data. This is a general concern in nanotoxicol ogy and more research coherence is required for produ cing meaningful results. In a recent review, Kim and Ryu identified increased oxidative stress, apoptosis and genotoxicity to be the main in vitro outcomes upon exposure to AgNPs. The major drawback was that the investigated AgNPs were different in each study. i. e.

manufactured in different ways, more or less purified, with various size distributions Inhibitors,Modulators,Libraries and coatings, tested on different cell Inhibitors,Modulators,Libraries lines under different cell culture condi tions, and often without the use of reference materials. Moreover, there was in general a lack of thorough characterization of the AgNPs in cell medium. In all, with contradictory findings reported, there is at present no general agreement on the in vitro toxicity of AgNPs. A study by Hackenberg et al. reported reduced cell viability at a AgNP dose of 10 ugmL in human mesenchymal stem cells, whereas Samberg et al. showed no toxicity for progeni tor human adipose derived stem cells up to 100 ugmL. Also, the stability and aging of AgNPs have been reported to be important for the Inhibitors,Modulators,Libraries toxicological outcome. Kittler et al.

showed a significant increase in toxicity following storage of AgNPs up to 6 months and this was correlated with the release of Ag ions. Ul timately, Inhibitors,Modulators,Libraries the synthesis method and the presence of re sidual contaminants could also account for the observed toxicity. In addition to reported variations in cytotoxicity, there is a lack of Inhibitors,Modulators,Libraries consensus on the underlying mechanisms that drive the toxicity of AgNPs the particles per se, the released Ag ionic species, or their combination. For example, Beer et al. suggested that the cytotoxic effects of AgNPs, following exposure of A549 cells, were largely explained by released Ag ions. In a follow up study, the global gene expression profiling in the same cell line suggested that even though the responses to Ag ions and AgNPs were related as regards effects such as induction of metallothioneins, the AgNPs ultimately af fected the cells in a more complex way.

We recently showed that the cellular uptake of Ag was significantly higher when cells were exposed to Ag as NPs rather than ions. Thus, there is emerging evidence for the Trojan horse hypothesis according to which the particle medi ates the AgNPs uptake via endocytosis Ivacaftor clinical thereby increas ing the intracellular bioavailability of Ag. Some previous studies have focused on investigating size dependent ef fects of AgNPs. However, whereas for example Liu et al.