Multiparametric investigation of non functionalized-AGuIX nanoparticles in 3D human airway epithelium models demonstrate
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Journal of Nanobiotechnology Open Access
RESEARCH
Multiparametric investigation of non functionalized‑AGuIX nanoparticles in 3D human airway epithelium models demonstrates preferential targeting of tumor cells Lucie Sancey1* , Odile Sabido2,3, Zhiguo He3,4, Fabien Rossetti5, Alain Guignandon6,3, Valérie Bin2,3, Jean‑Luc Coll1, Michèle Cottier2,3,7, François Lux5,8,9, Olivier Tillement5,8, Samuel Constant10,11, Christophe Mas11 and Delphine Boudard2,3,7*
Abstract 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 tumorbearing 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 A GuIX® NPs upon radiation exposure in this model. In conclusion, 3D cell cultures can efficiently mimic the normal and tumorbearing airway epitheliums, providing an ethical and accessible model for the investigation of nebulized NPs. Keywords: AGuIX® nanoparticles, 3D human healthy and tumor airway models, Nanoparticle’s toxicity, Nanoparticle’s uptake, Tumor targeting Background Non-small-cell lung cancer (NSCLC) is the principal type of lung cancer for the respiratory tract (85%), for which the standard treatment is surgery, especially for patients with early-stage NSCLC. However, some patients are not eligible for surgery because of medical comorbidities. In such cases, radiotherapy is an option that should be considered, in particular for early-stage, node-negative *Correspondence: lucie.sancey@univ‑grenoble‑alpes.fr; delphine. boudard@univ‑st‑etienne.fr 1 Institute for Advanced Biosciences, INSERM U1209, CNRS, UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France 2 INSERM U1059, Laboratoire SAINBIOSE, équipe DVH/PIB, Faculté de Médecine, Université Jean Monnet, Saint‑Etienne, France Full list of author information is available at the end of the article
patients [1]. The standard of care recommendations promote the stereotactic radiation (SR) approach, a modality able to precisely deliver high-dose fractions to a small target or volume of disease, thereby reducing the dose or sparing healthy tissues [2]. Among SR approaches, image-guided radiation therapy (IGRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) constitute recent methods aimed at improving the efficacy of radiotherapy [3]. Despite these improvements, the main constraint is limiting toxicity in healthy tissues that should be spared. Therefore, the use of ra
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