Translocation de nanoparticules d'oxyde métallique au travers de la barrière respiratoire

The widespread use of nanoparticles (NPs) in many fields involves evaluating their potential adverse effects on human health. The respiratory tract represents the major route of exposure after NP exposure. In this context, our aim was the evaluation of NP translocation across an in vitro human bronchial epithelial monolayer in function of their physic-chemical characteristics and the state of epithelial integrity. For this purpose we used fluorescently labeled metal oxide NPs of different chemical composition, size and surface charges. Three cellular models (the human bronchial Calu-3 and NCI-H292 and alveolar A549 cell lines) were tested and the Calu-3 model appears to be the most appropriated for in vitro development of a tight epithelium after culture in a two compartments chamber. We have demonstrated that all NPs could translocate through transcytosis according to their NP physico-chemical characteristics. Indeed we have determined that: i) Smaller NPs cross more than the larger ones, ii) Negative NP translocation is higher than for positive NPs and iii) Protein or lipid corona formation around NPs induce a modulation of the translocation. The state of integrity of the epithelial monolayer is also an important issue for NP translocation. Epithelial tight junction opening after an inflammatory context led to a significant increase of NP passage through the paracellular route. In conclusion, this study have demonstrated the NP capacity to translocate across epithelial barriers and the interest to develop in vitro cellular models for studying the importance of NP physico-chemical characteristics as well as the state of integrity of the monolayer in this mechanism.