Multimodal approach to nanoparticle toxicity assessment (conceptual framework for in vitro to in vivo extrapolation)

This study proposes a novel multimodal framework for assessing the time-dependent toxicity of iron oxide nanoparticles (SPIONs), aiming to improve in vitro to in vivo extrapolation (IVIVE). The framework integrates experimental data from Caco-2 cells and C. elegans with sequential mathematical modeling and neural network analysis. By accounting for complex, time-dependent processes such as cellular uptake, intracellular transport, and SPION degradation, this approach addresses the unique toxicological profile of nanoparticles. In vitro experiments evaluated cytotoxicity, reactive oxygen species (ROS) production, and antioxidant enzyme expression over 96 hours, revealing strong correlations between nanoparticle uptake, iron levels, oxidative stress, and cell viability. Mathematical models, validated against experimental data, enable the calculation of IC50 values and facilitate interspecies extrapolation. This integrated methodology, achieving an R² > 0.85 for predictive correlations, holds significant promise for reducing reliance on animal testing in future nanotoxicity evaluations.