Molecular modeling of interaction between lipid monolayer and graphene nanosheets: implications for pulmonary nanotoxicity and pulmonary drug delivery

Understanding how nanoparticles interact with the pulmonary surfactant monolayer (PSM) is of great importance for safe applications in biomedicine and for evaluation of both health and environment impacts. Here, by performing molecular dynamics simulations, we propose a possible origin of the pulmonary nanotoxicity of graphene-based nanoparticles that comes from a rigidifying effect of graphene nanosheets (GNs) on PSM. This, in reality, indicates that once captured by the PSM, inhaled GNs are hard to be removed from the PSM partially because the expiration or PSM compression is locally restrained, possibly leading to GN accumulation on the PSM. The local rigidifying effect, which is enhanced as multiple GNs approach each other, is found to be dependent on the GN hydrophobicity. In the expiration or PSM compression process, the hydrophilic GN keeps adhering to the monolayer-air interface, while the hydrophobic GN tends to be hosted in the hydrophobic interior and internalize into the PSM via self-rotation. Besides the spontaneous internalization via PSM compression, our pulling simulations indicate that both pulmonary internalization and externalization of GNs can be accomplished by direct translocation across the PSM. The effect of GN hydrophobicity on the direct PSM translocation is well supported by the free energy analysis. This work will help our understanding of pulmonary nanotoxicity of GNs and provide useful guidelines for molecular design of GN-based pulmonary drug delivery materials.