Abstract
It has been demonstrated that certain engineered nanomaterials (ENMs) could induce chronic lung inflammation and fibrosis, however, the key structure activity relationships (SARs) that the link the physicochemical properties and the fibrogenic effects have not been thoroughly reviewed. Recently, significant progress has been made in our understanding of the SAR, and it has been demonstrated that ENMs including rare earth oxides (REOs), graphene and graphene oxides (GO), fumed silica, as well as high aspect ratio materials (such as CNTs and CeO(2) nanowires etc.) could trigger the NLRP3 inflammasome activation and IL-1β production in macrophages and subsequent series of profibrogenic cytokines, i.e. TGF-β1 and PDGF-AA in vitro and in vivo, resulting in synergistically cell-cell communication among macrophages, epithelial cells, and fibroblasts in a process named epithelial-mesenchymal transition (EMT) and collagen deposition in the lung as the adverse outcomes. Interestingly, different ENMs engage a range of distinct pathways leading to the NLRP3 inflammasome activation and IL-1β production in macrophages, which include frustrated phagocytosis, physical piercing, plasma membrane perturbation or damage to lysosomes due to high aspect ratio, particle structure, surface reactivity, transformation, etc. Furthermore, ENM's properties determine the biopersistence in vivo, which also play a major role in chronic lung fibrosis. Based on these progresses, we reviewed recent findings in the literature on the major SARs leading to chronic lung effects.