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

Toxics

Carole Ronzani¹  Yasmin Arezki¹  Françoise Pons¹  Juliette Cornacchia¹  Luc Lebeau¹  Mickaël Rapp¹ 

[1] Laboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, 67400 Illkirch, France;

关键词: co-culture model;    multi-endpoint approach;    nanoparticles;    carbon dots;    nanotoxicology;    lung toxicity;   

DOI  :  10.3390/toxics9090210

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown