title: Functionalization of carbon nanoparticles modulates inflammatory cell recruitment and NLRP3 inflammasome activation.
abstract: The inflammatory effects of carbon nanoparticles (NPs) are highly disputed. Here it is demonstrated that endotoxin-free preparations of raw carbon nanotubes (CNTs) are very limited in their capacity to promote inflammatory responses in vitro, as well as in vivo. Upon purification and selective oxidation of raw CNTs, a higher dispersibility is achieved in physiological solutions, but this process also enhances their inflammatory activity. In synergy with toll-like receptor (TLR) ligands, CNTs promote NLRP3 inflammasome activation and it is shown for the first time that this property extends to spherical carbon nano-onions (CNOs) of 6 nm in size. In contrast, the benzoic acid functionalization of purified CNTs and CNOs leads to significantly attenuated inflammatory properties. This is evidenced by a reduced secretion of the inflammatory cytokine IL-1β, and a pronounced decrease in the recruitment of neutrophils and monocytes following injection into mice. Collectively, these results reveal that the inflammatory properties of carbon NPs are highly dependent on their physicochemical characteristics and crucially, that chemical surface functionalization allows significant moderation of these properties.
authors.affiliation: Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College, Dublin 2, Ireland; Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin 2, Ireland.
authors.forename: Marie
authors.initials: M
authors.lastname: Yang
authors.forename: Kevin
authors.initials: K
authors.lastname: Flavin
authors.forename: Ilona
authors.initials: I
authors.lastname: Kopf
authors.forename: Gabor
authors.initials: G
authors.lastname: Radics
authors.forename: Claire H A
authors.initials: CH
authors.lastname: Hearnden
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: McManus
authors.forename: Barry
authors.initials: B
authors.lastname: Moran
authors.forename: Adrian
authors.initials: A
authors.lastname: Villalta-Cerdas
authors.forename: Luis A
authors.initials: LA
authors.lastname: Echegoyen
authors.forename: Silvia
authors.initials: S
authors.lastname: Giordani
authors.forename: Ed C
authors.initials: EC
authors.lastname: Lavelle
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells; D002352:Carrier Proteins / Q000737:chemistry*; D020170:Caspase 1 / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007249:Inflammation / Q000473:pathology*; D008024:Ligands; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry; D013499:Surface Properties
chemical_list: D002352:Carrier Proteins; D008024:Ligands; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D037742:Nanotubes, Carbon; D020170:Caspase 1; D010100:Oxygen
keywords: NLRP3 inflammasome; carbon nano-onions; carbon nanotubes; chemical functionalization; inflammation