Abstract
The peripheral lungs are a potential entrance portal for nanoparticles into the human body due to their large surface area. The fact that nanoparticles can be deposited in the alveolar region of the lungs is of interest for pulmonary drug delivery strategies and is of equal importance for toxicological considerations. Therefore, a detailed understanding of nanoparticle interaction with the structures of this largest and most sensitive part of the lungs is important for both nanomedicine and nanotoxicology. Astonishingly, there is still little known about the bio-nano interactions that occur after nanoparticle deposition in the alveoli. In this study, we compared the effects of surfactant-associated protein A (SP-A) and D (SP-D) on the clearance of magnetite nanoparticles (mNP) with either more hydrophilic (starch) or hydrophobic (phosphatidylcholine) surface modification by an alveolar macrophage (AM) cell line (MH-S) using flow cytometry and confocal microscopy. Both proteins enhanced the AM uptake of mNP compared with pristine nanoparticles; for the hydrophilic ST-mNP, this effect was strongest with SP-D, whereas for the hydrophobic PL-mNP it was most pronounced with SP-A. Using gel electrophoretic and dynamic light scattering methods, we were able to demonstrate that the observed cellular effects were related to protein adsorption and to protein-mediated interference with the colloidal stability. Next, we investigated the influence of various surfactant lipids on nanoparticle uptake by AM because lipids are the major surfactant component. Synthetic surfactant lipid and isolated native surfactant preparations significantly modulated the effects exerted by SP-A and SP-D, respectively, resulting in comparable levels of macrophage interaction for both hydrophilic and hydrophobic nanoparticles. Our findings suggest that because of the interplay of both surfactant lipids and proteins, the AM clearance of nanoparticles is essentially the same, regardless of different intrinsic surface properties.
Highlights
Because of the potential use of nano-sized particulate systems for pharmaceutical or medical purposes, the inhalation and pulmonary deposition of nanoparticles is a vigorously discussed topic among nanomedicine researchers
All of the magnetite nanoparticles (mNP) were composed of the same magnetic core material but were decorated either with hydrophilic or hydrophobic coatings
We found that surfactant protein D (SP-D) mainly triggered the cellular association of ST-mNP (Fig. 1A), whereas surfactant-associated protein A (SP-A) predominantly increased the interaction of the PL-mNPs with cells (Fig. 1B)
Summary
Because of the potential use of nano-sized particulate systems for pharmaceutical or medical purposes, the inhalation and pulmonary deposition of nanoparticles is a vigorously discussed topic among nanomedicine researchers. Non-cellular elements of the so-called air-blood barrier may play a key role here because this is the first biological matter that contacts nanoparticles after inhalation and deposition in the lungs. In the peripheral deep lungs, the so-called alveolar lining fluid, an ultra-thin layer that consists of an aqueous hypophase and a surface-active lipid-protein mixture, known as pulmonary surfactant, covers the epithelial cells. The pulmonary surfactant is continuous and spreads form the distal to the proximal lungs, where it is positioned at the air-interface making it the most outer part of the air-blood barrier [8,9]
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