A Co-Culture Model of the Human Respiratory Tract to Discriminate the Toxicological Profile of Cationic Nanoparticles According to Their Surface Charge Density

• Main Authors: Yasmin Arezki, Juliette Cornacchia, Mickaël Rapp, Luc Lebeau, Françoise Pons, Carole Ronzani
• Format: Article
• Language: English
• Published: MDPI AG 2021-08-01
• Series: Toxics
• Subjects: co-culture model; multi-endpoint approach; nanoparticles; carbon dots; nanotoxicology; lung toxicity
• Online Access: https://www.mdpi.com/2305-6304/9/9/210

This study aimed at discriminating with sensitivity the toxicological effects of carbon dots (CDs) with various zeta potential (ζ) and charge density (Q_ek) in different cellular models of the human respiratory tract. One anionic and three cationic CDs were synthetized as follows: CD-COOH (ζ = −43.3 mV); CD-PEI600 (Q_ek = 4.70 µmol/mg; ζ = +31.8 mV); CD-PEHA (Q_ek = 3.30 µmol/mg; ζ = +29.2 mV) and CD-DMEDA (Q_ek = 0.01 µmol/mg; ζ = +11.1 mV). Epithelial cells (A549) and macrophages (THP-1) were seeded alone or as co-cultures with different A549:THP-1 ratios. The obtained models were characterized, and multiple biological responses evoked by CDs were assessed in the mono-cultures and the best co-culture model. With 14% macrophages, the 2:1 ratio co-culture best mimicked the in vivo conditions and responded to lipopolysaccharides. The anionic CD did not induce any effect in the mono-cultures nor in the co-culture. Among the cationic CDs, the one with the highest charge density (CD-PEI600) induced the most pronounced responses whatever the culture model. The cationic CDs of low charge density (CD-PEHA and CD-DMEDA) evoked similar responses in the mono-cultures, whereas in the co-culture, the three cationic CDs ranked according to their charge density (CD-PEI600 > CD-PEHA > CD-DMEDA), when taking into account their inflammatory effect. Thus, the co-culture system developed in this study appears to be a sensitive model for finely discriminating the toxicological profile of cationic nanoparticles differing by the density of their surface charges.