MnOx nanoparticles cause broad transcriptomic deregulation in A549 cells, unlike graphene-MnOx composites

Abstract Nanomaterials (NMs) pose significant, yet unknown, occupational health risks owing to their nanoscale size and reactivity, particularly through inhalation. Considering this primary exposure route, we investigated the toxicological response of A549 human lung epithelial cells using toxicotranscriptomics. These cells were exposed to free manganese oxide nanoparticles (MnOx NPs) and pristine or degraded graphene MnOx-nanocomposites. Our transcriptomics analysis revealed a stark contrast in the responses between the two material forms. MnOx NPs (GNA35) caused broad and extensive transcriptomic deregulation across multiple pathways, including significant enrichment in processes related to cellular stress, and apoptosis. Conversely, pristine and degraded graphene-MnOx nanocomposites (GNA15 and GNA15d) induced only minimal and limited transcriptional responses, indicating a substantially reduced toxicity profile. This transcriptional evidence demonstrates that the metal immobilization of MnOx NPs on a graphene surface effectively mitigates their intrinsic toxicological activity. Furthermore, the lack of enhanced toxicity upon degradation suggests that the composite maintains its protective capacity. These findings strongly indicate that incorporating metal-based NMs, such as MnOx, into a graphene composite notably enhances their safety profile for occupational handling.