Using in vitro studies, the responses of different cell types after exposure or uptake of silver nanoparticles in the cell can be studied in detail. Silver nanoparticles are able to release silver ions outside and/or inside a cell leading to the generation of oxidative stress, dose-dependent reduced cell division or ultimately to cell death.

Typically in the lab different cell lines are used as representative models for the respective routes of exposure under investigation (lung, skin, gastrointestinal tract, see also section "Uptake") or as models for various target organs (see article "Behaviour inside the Body"). These in vitro studies showed a dose-dependent effect of silver nanoparticles similar to the results obtained in animal experiments (in vivo studies). Besides cellular shrinkage and cell death (apoptosis) the generation of inflammation markers and the formation of reactive oxygen species (ROS) (oxidative stress) could be detected as well as further activation of stress signalling pathways within the cells.[1-16]


Cellular reaction and response to silver nanoparticle exposure. © Verano-Braga, T et al. (2014)Cellular reaction and response to silver nanoparticle exposure. © Verano-Braga, T et al. (2014)It is still an open question whether it is the silver nanoparticles or rather the released silver ions or even both which are responsible for the aforementioned effects. In an aqueous environment (e.g. in in vitro experiments or in the body) you will always find dissolved silver ions together with surface-bound ionic silver in addition to the silver nanoparticles. As silver ions are very reactive and would favour the formation of ROS, they will equally interact with, and bind rapidly to, other groups (ions, sulphur groups, proteins) thus being converted into "neutral" complexes. The desired amount of released silver ions can be easily altered by specifically adapting the size and surface properties (coating) of the silver nanoparticles.[17,7,12]


The majority of the in vitro studies support the "Trojan Horse" hypothesis, in which the release of silver ions only happens after intracellular uptake of the silver nanoparticles subsequently triggering the effects described (stress responses, cell death). The acidic environment within the cellular vesicles favours the dissolution of the nanoparticles. Therefore, researchers advocate to not only analyse the silver nanoparticle suspensions in in vitro experiments but also the nanoparticle-free supernatant in order to correlate the observed effects more accurately.[15,15,3]


"Trojan Horse" hypothesis for the mode of action of silver nanoparticles in cells. Adapted from Quadros et al. 2011"Trojan Horse" hypothesis for the mode of action of silver nanoparticles in cells. Adapted from Quadros et al. 2011

Depending on the type of silver nanoparticles used, some studies were able to directly link ROS formation and toxicity, whilst in other investigations ROS production and cell damage were only detectable after cellular uptake. In another analysis the silver nanoparticles activated cellular anti-oxidative protection mechanisms upon uptake thereby protecting the cell from oxidative damage. Oxidative DNA damage occurred only at very high doses which in turn further strengthened the "Trojan Horse" hypothesis.[4,5,14,6,13,7,12,2]


By releasing ions, silver nanoparticles are very effective against microorganisms and therefore are often used in medicine, e.g. in wound dressings or for spray disinfectants. However, comparative studies have shown that only a relatively small therapeutic window exists for the use of silver nanoparticles in wound dressing materials, in which the nanoparticles effectively kill the undesirable pathogens and act not toxic to the cells.[9,8,11]


The various studies have shown that relatively high concentrations of nano silver act negatively towards cellular health. As the size and surface coating of the silver nanoparticles generally have a strong influence on the nanoparticles' dissolution rate, bioavailability and distribution in the body, these properties can be altered specifically for the intended application and also to avoid undesirable side effects.



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