Carbon Nanotubes under Scrutiny: Their Toxicity and Utility in Mesothelioma Research

Abstract

Research on the toxicity of engineered carbon nanotubes (CNT) was initiated by Belgian academic chemists and toxicologists more than 15 years ago. It is now undisputed that some of these attractive nanomaterials induce serious illness such as fibrosis and cancer. The physico-chemical determinants of CNT-induced adverse effects are now elucidated and include shape, nanoscale diameter, and structural defects. Generated in vitro and in vivo data on their inflammogenic and fibrogenic activities were combined and translated in AOP (adverse outcome pathways) available for risk assessment and regulatory policies. The asbestos-like carcinogenic effect of CNT, notably their capacity to induce malignant mesothelioma (MM), remain, however, a cause of concern for public health and strongly curb the craze for CNT in industries. MM still represents a real challenge for clinicians and a highly refractory cancer to existing therapeutic strategies. By comparing mesotheliomagenic CNT (needle-like CNT-N) to non mesotheliomagenic CNT (tangled-like CNT-T), our group generated a relevant animal model that highlights immune pathways specifically associated to the carcinogenic process. Evidence indicates that only CNT-N possess the intrinsic capacity to induce a preferential, rapid, and sustained accumulation of host immunosuppressive cells that subvert immune surveillance and suppress anti-mesothelioma immunity. This new concept offers novel horizons for the clinical management of mesothelioma and represents an additional tool for predicting the mesotheliomagenic activity of newly elaborated CNT or nanoparticles.