The toxicity of nanoparticles and their interaction with cells: an in vitro metabolomic perspective

Nowadays, nanomaterials (NMs) are widely present in daily life due to their significant benefits, as demonstrated by their application in many fields such as biomedicine, engineering, food, cosmetics, sensing, and energy. However, the increasing production of NMs multiplies the chances of their release into the surrounding environment, making human exposure to NMs inevitable. Currently, nanotoxicology is a crucial field, which focuses on studying the toxicity of NMs. The toxicity or effects of nanoparticles (NPs) on the environment and humans can be preliminary assessed in vitro using cell models. However, the conventional cytotoxicity assays, such as the MTT assay, have some drawbacks including the possibility of interference with the studied NPs. Therefore, it is necessary to employ more advanced techniques that provide high throughput analysis and avoid interferences. In this case, metabolomics is one of the most powerful bioanalytical strategies to assess the toxicity of different materials. By measuring the metabolic change upon the introduction of a stimulus, this technique can reveal the molecular information of the toxicity induced by NPs. This provides the opportunity to design novel and efficient nanodrugs and minimizes the risks of NPs used in industry and other fields. Initially, this review summarizes the ways that NPs and cells interact and the NP parameters that play a role in this interaction, and then the assessment of these interactions using conventional assays and the challenges encountered are discussed. Subsequently, in the main part, we introduce the recent studies employing metabolomics for the assessment of these interactions in vitro.