Cellular toxicity of inorganic nanoparticles: Common aspects and guidelines for improved nanotoxicity evaluation

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

“…Furthermore the possibility of upscaling and automation of the execution, detection and data processing make these assays highly convenient with regard to a future high content screening approach for every newly synthetized NP 83,84 . Another popular approach is staining the entire cell or specific cellular components with cellular dyes, fluorescently labeled antibodies (AB) or molecular probes, which will interact with a specific biomolecule 40,78,85 . The samples can on the one hand be analyzed using a plate reader, but if information is requested on the variation between different cell types or status (e.g.…”

“…For example, ion leaching can either be detected in cell-free conditions using specialized buffers (pH 7.4; 5.5 and 4.5) and the intactness of stem cell functionality can be evaluated by observing the efficiency of cellular differentiation induced by specific protocols 40,92 .…”

“…Furthermore NP tend to behave differently in dispersion in comparison to chemicals as some are prone to degradation, agglomeration or aggregation and sedimentation, influencing NP uptake and subsequently NP toxicity 35,40,41 . Since these effects, as well as other adverse effects, are highly dependent on the physicochemical properties of the NP a thorough characterisation in both the dry state and in suspension is an absolute necessity to interpret results and formulate conclusions on the correlations between the NP's properties and the observed effects 29,42 .…”

“…From these issues it can be deducted that nanotoxicity assessment can often be more complex than toxicity testing of chemical substances. It is known that most chemicals induce toxicological responses through interaction with specific biomolecules whereas a single type of NP may cause toxicity via a combination of different mechanisms like the induction of reactive oxygen species (ROS), genotoxicity, morphological modifications, NP degradation and immunological effects 31,40,43 .…”

“…After endocytosic uptake, the NP are exposed to an oxidative environment in late endosomes or lysosomes. Here they face degrading enzymes like cathepsin L and a pH of 5.9 in late endosomes or 4.5 in lysosomes 40,62 . This might cause degradation or dissolution of the NP resulting in the leaching of free ions 40 .…”