Effect of pulmonary surfactant on the dissolution, stability and uptake of zinc oxide nanowires by human respiratory epithelial cells

Abstract

Inhaled nanoparticles (NPs) have high-deposition rates in the alveolar region of the lung but the effects of pulmonary surfactant (PS) on nanoparticle bioreactivity are unclear. Here, the impact of PS on the stability and dissolution of ZnO nanowires (ZnONWs) was investigated, and linked with their bioreactivity in vitro with human alveolar epithelial type 1-like cells (TT1). Pre-incubation of ZnONWs with Curosurf® (a natural porcine PS) decreased their dissolution at acidic pH, through the formation of a phospholipid corona. Confocal live cell microscopy confirmed that Curosurf® lowered intracellular dissolution, thus delaying the onset of cell death compared to bare ZnONWs. Despite reducing dissolution, Curosurf® significantly increased the uptake of ZnONWs within TT1 cells, ultimately increasing their toxicity after 24 h. Although serum improved ZnONW dispersion in suspension similar to Curosurf®, it had no effect on ZnONW internalization and toxicity, indicating a unique role of PS in promoting particle uptake. In the absence of PS, ZnONW length had no effect on dissolution kinetics or degree of cellular toxicity, indicating a less important role of length in determining ZnONW bioreactivity. This work provides unique findings on the effects of PS on the stability and toxicity of ZnONWs, which could be important in the study of pulmonary toxicity and epithelial-endothelial translocation of nanoparticles in general.

Keywords:

• Alveoli
• Curosurf®
• epithelial uptake
• nanoparticles
• nanotoxicity

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. This work was funded in part by a grant from the NIEHS (grant number U19ES019536) and the US EPA/NERC (EPA STAR RD83469301 and NERC), a Leverhulme Trust grant and an ERC starting grant to A.E.P. (# 257182). I.G.T. acknowledges a Wellcome Trust grant. The authors acknowledge Prof. Milo S.P. Shaffer for the helpful discussions.

Supplementary material available online

Figures S1, S4, S5, S6, S7, S8, S9 and S10