The role of nanoparticle shape in translocation across the pulmonary surfactant layer revealed by molecular dynamics simulations

Abstract

Airborne nanoparticles (NPs), which vary widely in both shape and size, can be inhaled and deposit in the alveolar region, where they first interact with the pulmonary surfactant (PS) layer to cause toxicological effects and impact the subsequent fate of NPs inside the body. Previous studies on NP–PS interactions have been conducted focusing on spherical NPs, thereby overlooking the role of NP shape. Here, we demonstrate by molecular dynamics simulations the translocation of NPs across the PS layer being influenced by the NP shape. It was found that hydrophilic NPs with all dimensions smaller than 5 nm can rapidly penetrate through the PS layer, being barely affected by the NP shape, while the shape matters for larger NPs in both translocation and PS perturbation. For hydrophobic NPs with at least one dimension smaller than the PS layer thickness, they prefer to be immersed into but hardly transported across the PS layer. If at least one dimension is larger than the PS layer thickness, they can be readily wrapped by the layer under compression, with the steady wrapping state being dominated by the shape-dependent NP rotation. During transport, PS molecules can be recruited by NPs, acting as a corona to influence the biological identity of NPs. Adversely, PS depletion can be induced, together with the perturbed PS arrangement around sharp NP edges to cause destructive PS layer rupture. Our results suggest that all studies of inhalation toxicity and pulmonary drug delivery should consider first the interactions of target NPs with the PS layer, where the shape significantly matters.