56th Eurotox Conference - Personalized nano-immunotoxicology for the workplace
In vitro immuno-nanotoxicological methods that take pre-existing conditions into account
In the workplace environment, where nanoparticles (NPs) may reach higher concentrations, the co-existence of allergens may result in new combinations of NPs with allergens. Normal as well as pre-disposed individuals, suffering from pre-existing allergic sensitization, may thus be affected by inhalation of aerosols carrying these new combinations having different immunological consequences. Recently, epithelial barrier integrity has been recognized to exert major impacts on the general health status of humans (epithelial barrier hypothesis, https://doi.org/10.1038/s41577-021-00538-7), responsible for increase in allergy, autoimmunity and other chronic conditions. Moreover, for therapeutic approaches allergens are conjugated with different types of particulate matter, which serve as adjuvants, to boost the immune reaction or, in the particular case of allergen-specific immunotherapy, to drive immunomodulation from a type 2 to a more tolerogenic response. Here, the variety of materials can range from classical alum-based to more sophisticated nanovaccine carriers. Decreasing the size-range into the nano-scale goes in line with specific surface-related effects, known as protein corona formation, having impact not just on the NP itself, but even more importantly on the bound allergen. We have recently established a suite of in vitro assays that elucidate effects at a structural and molecular level with a particular focus on responses specific for sensitized individuals, to sort out alterations in the allergic effector function. Data enrichment from in vitro experimentation may be accomplished by use of suitable in silico modeling tools. Therefore, protein corona prediction was tested and evaluated for its potential to complement the experimental workflow. Ultimately, combined in vitro and in silico data including comprehensive metadata was uploaded to the NanoCommons Knowledge Base to aid data FAIRness, i.e. Findability, Accessibility, Interoperability, and Reusability. In conclusion, such integrated workflows can help in early-stage decision-making processes in therapeutic development, and hence, promote safe-by design approaches in nanomedical innovation, as well as – in combination with in silico-based exposure-relevant dose-finding – serve for risk monitoring at specifically loaded areas, e.g., workplaces, taking into account pre-existing conditions such as allergic sensitization. Acknowledgments: This work was supported by the international PhD program “Immunity in Cancer and Allergy - ICA” of the Austrian Science Fund (FWF, grant no. W01213), the EU H2020 projects NanoRigo and NanoCommons (grant no.s 814530 and 731032, respectively), and the Allergy-Cancer-BioNano (ACBN) Research Center of the Paris Lodron University of Salzburg (PLUS).