Functionalization of Carbon Nanoparticles Modulates Inflammatory Cell Recruitment and NLRP3 Inflammasome Activation

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. The inflammatory properties of carbon nanoparticles are regarded as a major roadblock in their use for biomedical applications. A simple and reproducible strategy is described to address this issue using a novel purification process combined with surface chemical functionalization. This is also the first report that single walled carbon nanotubes and carbon nano‐onions have the ability to activate the NLRP3 inflammasome.