Multiparametric investigation of non functionalized-AGuIX nanoparticles in 3D human airway epithelium models demonstrates preferential targeting of tumor cells

Lucie Sancey (1) , Odile Sabido (2) , Zhiguo He (3) , Fabien Rossetti (4) , Alain Guignandon (2) , Valérie Bin (2) , Jean-Luc Coll (1) , Michèle Cottier (2) , François Lux (4, 5) , Olivier Tillement (4, 5) , Samuel Constant (6) , Christophe Mas (7) , Delphine Boudard (2, 8)

1 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
2 SAINBIOSE - Santé Ingénierie Biologie Saint-Etienne
3 BIIO - Biologie, Ingénierie et Imagerie pour l'Ophtalmologie
4 iLM - FENNEC - iLM - Formation, élaboration de nanomatériaux et cristaux
5 NH TherAguix SA [Meylan]
6 Epithelix SARL [Geneva, Switzerland]
7 OncoTheis SARL [Geneva, Switzerland]
8 UF 6725 - UF 6726 - Service de Cytologie - Histologie Rénale - Embryologie [CHU Saint-Etienne]

Liquid deposit mimicking surface aerosolization in the airway is a promising strategy for targeting bronchopulmonary tumors with reduced doses of nanoparticle (NPs). In mimicking and studying such delivery approaches, the use of human in vitro 3D culture models can bridge the gap between 2D cell culture and small animal investigations. Here, we exposed airway epithelia to liquid-apical gadolinium-based AGuIX ® NPs in order to determine their safety profile. We used a multiparametric methodology to investigate the NP's distribution over time in both healthy and tumor-bearing 3D models. AGuIX ® NPs were able to target tumor cells in the absence of specific surface functionalization, without evidence of toxicity. Finally, we validated the therapeutic potential of this hybrid theranostic AGuIX ® NPs upon radiation exposure in this model. In conclusion, 3D cell cultures can efficiently mimic the normal and tumor-bearing airway epitheliums, providing an ethical and accessible model for the investigation of nebulized NPs.

Mots clés: AGuIX ® nanoparticles; 3D human healthy and tumor airway models; Nanoparticle's toxicity; Nanoparticle's uptake; Tumor targeting

Domaines: Sciences du Vivant [q-bio]; Biotechnologies

Lucie Sancey, Odile Sabido, Zhiguo He, Fabien Rossetti, Alain Guignandon, et al.. Multiparametric investigation of non functionalized-AGuIX nanoparticles in 3D human airway epithelium models demonstrates preferential targeting of tumor cells. Journal of Nanobiotechnology, 2020, 18 (1), pp.129. ⟨10.1186/s12951-020-00683-6⟩. ⟨inserm-02941434⟩