Maud Weiss1, Jiahui Fan1, Mickaël Claudel1, Thomas Sonntag1, Pascal Didier2, Carole Ronzani1, Luc Lebeau1, Françoise Pons3,4. 1. Laboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, Illkirch, France. 2. Laboratoire de Bioimagerie et Pathologies, Faculté de Pharmacie, UMR 7021, CNRS-Université de Strasbourg, Illkirch, France. 3. Laboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, Illkirch, France. pons@unistra.fr. 4. Faculté de Pharmacie, UMR 7199, 74 route du Rhin, 67400, Illkirch, France. pons@unistra.fr.
Abstract
BACKGROUND: A positive surface charge has been largely associated with nanoparticle (NP) toxicity. However, by screening a carbon NP library in macrophages, we found that a cationic charge does not systematically translate into toxicity. To get deeper insight into this, we carried out a comprehensive study on 5 cationic carbon NPs (NP2 to NP6) exhibiting a similar zeta (ζ) potential value (from + 20.6 to + 26.9 mV) but displaying an increasing surface charge density (electrokinetic charge, Qek from 0.23 to 4.39 µmol/g). An anionic and non-cytotoxic NP (NP1, ζ-potential = - 38.5 mV) was used as control. RESULTS: The 5 cationic NPs induced high (NP6 and NP5, Qek of 2.95 and 4.39 µmol/g, respectively), little (NP3 and NP4, Qek of 0.78 and 1.35 µmol/g, respectively) or no (NP2, Qek of 0.23 µmol/g) viability loss in THP-1-derived macrophages exposed for 24 h to escalating NP dose (3 to 200 µg/mL). A similar toxicity trend was observed in airway epithelial cells (A549 and Calu-3), with less viability loss than in THP-1 cells. NP3, NP5 and NP6 were taken up by THP-1 cells at 4 h, whereas NP1, NP2 and NP4 were not. Among the 6 NPs, only NP5 and NP6 with the highest surface charge density induced significant oxidative stress, IL-8 release, mitochondrial dysfunction and loss in lysosomal integrity in THP-1 cells. As well, in mice, NP5 and NP6 only induced airway inflammation. NP5 also increased allergen-induced immune response, airway inflammation and mucus production. CONCLUSIONS: Thus, this study clearly reveals that the surface charge density of a cationic carbon NP rather than the absolute value of its ζ-potential is a relevant descriptor of its in vitro and in vivo toxicity.
BACKGROUND: A positive surface charge has been largely associated with nanoparticle (NP) toxicity. However, by screening a carbon NP library in macrophages, we found that a cationic charge does not systematically translate into toxicity. To get deeper insight into this, we carried out a comprehensive study on 5 cationic carbon NPs (NP2 to NP6) exhibiting a similar zeta (ζ) potential value (from + 20.6 to + 26.9 mV) but displaying an increasing surface charge density (electrokinetic charge, Qek from 0.23 to 4.39 µmol/g). An anionic and non-cytotoxic NP (NP1, ζ-potential = - 38.5 mV) was used as control. RESULTS: The 5 cationic NPs induced high (NP6 and NP5, Qek of 2.95 and 4.39 µmol/g, respectively), little (NP3 and NP4, Qek of 0.78 and 1.35 µmol/g, respectively) or no (NP2, Qek of 0.23 µmol/g) viability loss in THP-1-derived macrophages exposed for 24 h to escalating NP dose (3 to 200 µg/mL). A similar toxicity trend was observed in airway epithelial cells (A549 and Calu-3), with less viability loss than in THP-1 cells. NP3, NP5 and NP6 were taken up by THP-1 cells at 4 h, whereas NP1, NP2 and NP4 were not. Among the 6 NPs, only NP5 and NP6 with the highest surface charge density induced significant oxidative stress, IL-8 release, mitochondrial dysfunction and loss in lysosomal integrity in THP-1 cells. As well, in mice, NP5 and NP6 only induced airway inflammation. NP5 also increased allergen-induced immune response, airway inflammation and mucus production. CONCLUSIONS: Thus, this study clearly reveals that the surface charge density of a cationic carbon NP rather than the absolute value of its ζ-potential is a relevant descriptor of its in vitro and in vivo toxicity.
Authors: Marina E Vance; Todd Kuiken; Eric P Vejerano; Sean P McGinnis; Michael F Hochella; David Rejeski; Matthew S Hull Journal: Beilstein J Nanotechnol Date: 2015-08-21 Impact factor: 3.649