Redox Biology, Volume 47, November 2021,
Oxidation of engineered nanomaterials during application in various industrial sectors can alter their toxicity. Oxidized nanomaterials also have widespread industrial and biomedical applications. In this study, we evaluated the cardiopulmonary hazard posed by these nanomaterials using oxidized carbon black (CB) nanoparticles (CBox) as a model particle. Particle surface chemistry was characterized by X-ray photo electron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR). Colloidal characterization and in vitro dosimetry modeling (particle kinetics, fate and transport modeling) were performed. Lung inflammation was assessed following oropharyngeal aspiration of CB or oxidized CBox particles (20 μg per mouse) in C57BL/6J mice. Toxicity and functional assays were also performed on murine macrophage (RAW 264.7) and endothelial cell lines (C166) with and without pharmacological inhibitors. Oxidant generation was assessed by electron paramagnetic resonance spectroscopy (EPR) and via flow cytometry. Endothelial toxicity was evaluated by quantifying pro-inflammatory mRNA expression, monolayer permeability, and wound closure. XPS and FTIR spectra indicated surface modifications, the appearance of new functionalities, and greater oxidative potential (both acellular and in vitro) of CBox particles. Treatment with CBox demonstrated greater in vivo inflammatory potentials (lavage neutrophil counts, secreted cytokine, and lung tissue mRNA expression) and air-blood barrier disruption (lavage proteins). Oxidant-dependent pro-inflammatory signaling in macrophages led to the production of CXCR3 ligands (CXCL9,10,11). Conditioned medium from CBox-treated macrophages induced significant elevation in endothelial cell pro-inflammatory mRNA expression, enhanced monolayer permeability and impairment of scratch healing in CXCR3 dependent manner. In summary, this study mechanistically demonstrated an increased biological potency of CBox particles and established the role of macrophage-released chemical mediators in endothelial damage.
Animal; Animal Cell; Animal Experiment; Animal Model; Animal Tissue; Animals; Article; C57BL Mouse; CXCL11 Chemokine; CXCL9 Chemokine; Carbon Nanoparticle; Cardiotoxicity; Cell Damage; Chemical Analysis; Chemical Modification; Chemical Reaction Kinetics; Chemokine Receptor; Chemokine Receptor CXCR3; Controlled Study; Cytokine; Cytokine Release; Dosimetry; Electron Paramagnetic Spectroscopy; Electron Spin Resonance; Endothelial Cells; Endothelium Cell; Flow Cytometry; Fourier Transform Infrared Spectroscopy; Gamma Interferon Inducible Protein 10; Gene Expression; In Vitro Study; In Vivo Study; Lung; Lung Parenchyma; Lung Toxicity; Macrophage; Male; Messenger RNA; Mice; Mice, Inbred C57BL; Mouse; Nanoparticle; Nanoparticle Carbon Black; Nanoparticles; Neutrophil Count; Nonhuman; Oxidation Reduction Potential; Oxidized Carbon Black; Oxidized Carbon Black Nanoparticle; Ozone; Permeability; Pneumonia; Receptors, Chemokine; Signal Transduction; Soot; Spectroscopy; Surface Modification; Toxicity; Unclassified Drug; Wound Closure; X Ray Photoemission Spectroscopy; Global