Resolution of MoS 2 Nanosheets-induced Pulmonary Inflammation Driven by Nanoscale Intracellular Transformation and Extracellular-vesicle Shuttles.

Pulmonary exposure to some engineered nanomaterials can cause chronic lesions as a result of unresolved inflammation. Among two-dimensional (2D) nanomaterials and graphene, MoS 2 have received tremendous attention in optoelectronics and nanomedicine. Here we propose an integrated approach to follow up the transformation of MoS 2 nanosheets at the nanoscale and their impact on the lung inflammation status over one month after a single inhalation in mice. Analysis of immune cells, alveolar macrophages, extracellular vesicles, and cytokine profiling in bronchoalveolar lavage fluid (BALF) showed that MoS 2 nanosheets induced initiation of lung inflammation that was rapidly resolved despite the persistence of various biotransformed molybdenum-containing nanostructures in alveolar macrophages and extracellular vesicles up to one month. Using in situ liquid phase transmission electron microscopy experiments, we could evidence the dynamics of MoS 2 nanosheets transformation triggered by reactive oxygen species. Three main transformation mechanisms were observed directly at the nanoscale level: 1) scrolling of the dispersed sheets leading to the formation of nanoscrolls and folded patches, 2) etching releasing soluble MoO 4 - , and 3) oxidation generating oxidized sheet fragments. Extracellular vesicles released in BALF were also identified as a potential shuttle of MoS 2 nanostructures and their degradation products and more importantly as mediators of inflammation resolution. This article is protected by copyright. All rights reserved.