Toxicological response to nanomaterial exposure in in vitro lung cells are determined by cell-type.
Nanotechnology is an advancing field that continually introduces new nano-enabled products into consumer products thereby increasing the risk of nanoparticle exposure to humans and the surrounding environment. The increased rate of nanoparticle exposure to humans requires the field of nanotoxicology to rapidly screen for markers of toxicity after nanomaterial exposure. To properly screen for markers of toxicity, this study aims to address gaps in the in vitro nanotoxicology literature. First, the most common biochemical pathways investigated in the nanotoxicology literature were outlined to build a landscape of the in vitro nanotoxicology literature to find the gaps in the literature. Next, ill-defined cell culture parameters were examined to outline the appropriate methodology required to generate proper cytotoxicological models. Lastly, a suite of microscopy techniques was used to examine novel mechanisms through which aluminum (Al) nanomaterials exert their toxicity. Results showed that no two cell lines are alike as each cell-type exhibits differential baseline characteristics. Furthermore, the cell-type and inherent morphological and biochemical differences between all cells influences the toxicological response to nanomaterials. This research will advance the field of nanotoxicology by highlighting the importance of proper characterization for in vitro cell culture systems and nanoparticle test systems to increase the complexity and impact of conclusions drawn from past, current, and future pulmonary nanotoxicological studies.