Harmful at non-cytotoxic concentrations: SiO₂-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells

<p>The pulmonary delivery of nanoparticles (NPs) is a promising approach in nanomedicine. For the efficient and safe use of inhalable NPs, understanding of NP interference with lung surfactant metabolism is needed. Lung surfactant is predominantly a phospholipid substance, synthesized in alveolar type II cells (ATII), where it is packed in special organelles, lamellar bodies (LBs). <i>In vitro</i> and <i>in vivo</i> studies have reported NPs impact on surfactant homeostasis, but this phenomenon has not yet been sufficiently examined. We showed that in ATII-like A549 human lung cancer cells, silica-coated superparamagnetic iron oxide NPs (SiO₂-SPIONs), which have a high potential in medicine, caused an increased cellular amount of acid organelles and phospholipids. In SiO₂-SPION treated cells, we observed elevated cellular quantity of multivesicular bodies (MVBs), organelles involved in LB biogenesis. In spite of the results indicating increased surfactant production, the cellular quantity of LBs was surprisingly diminished and the majority of the remaining LBs were filled with SiO₂-SPIONs. Additionally, LBs were detected inside abundant autophagic vacuoles (AVs) and obviously destined for degradation. We also observed time- and dose-dependent changes in mRNA expression for proteins involved in lipid metabolism. Our results demonstrate that non-cytotoxic concentrations of SiO₂-SPIONs interfere with surfactant metabolism and LB biogenesis, leading to disturbed ability to reduce hypophase surface tension. To ensure the safe use of NPs for pulmonary delivery, we propose that potential NP interference with LB biogenesis is obligatorily taken into account.</p

Adsorption of Amino Acids, Aspartic Acid, and Lysine onto Iron-Oxide Nanoparticles

Understanding the adsorption of amino acids (AAs) onto magnetic iron-oxide nanoparticles (SPIONs) is important not only for the preparation of the aqueous suspensions, but also for understanding the interactions at the bionano interface. In this investigation the adsorption of aspartic acid (Asp) and lysine (Lys) onto SPIONs was studied, based on a characterization of the suspension properties, i.e., measurements of the ξ-potential, the hydrodynamic size, and the osmolality, and by direct HPLC analysis of the AA in the supernatants and at the nanoparticles of the ultracentrifuged suspensions. The results show that the AAs adsorb onto the SPIONs in the form of large molecular associates, which decisively influence the nanoparticles’ surface properties. A measurement of the freezing-point depression using a Knauer osmometer proved that the molecular associates are already formed in the AA aqueous solutions

Cellular Internalization of Dissolved Cobalt Ions from Ingested CoFe₂O₄ Nanoparticles: In Vivo Experimental Evidence

With a model invertebrate animal, we have assessed the fate of magnetic nanoparticles in biologically relevant media, i.e., digestive juices. The toxic potential and the internalization of such nanoparticles by nontarget cells were also examined. The aim of this study was to provide experimental evidence on the formation of Co²⁺, Fe²⁺, and Fe³⁺ ions from CoFe₂O₄ nanoparticles in the digestive juices of a model organism. Standard toxicological parameters were assessed. Cell membrane stability was tested with a modified method for measurement of its quality. Proton-induced X-ray emission and low energy synchrotron radiation X-ray fluorescence were used to study internalization and distribution of Co and Fe. Co²⁺ ions were found to be more toxic than nanoparticles. We confirmed that Co²⁺ ions accumulate in the hepatopancreas, but Fe^<i>n</i>+ ions or CoFe₂O₄ nanoparticles are not retained in vivo. A model biological system with a terrestrial isopod is suited to studies of the potential dissolution of ions and other products from metal-containing nanoparticles in biologically complex media

Cellular Internalization of Dissolved Cobalt Ions from Ingested CoFe₂O₄ Nanoparticles: In Vivo Experimental Evidence

With a model invertebrate animal, we have assessed the fate of magnetic nanoparticles in biologically relevant media, i.e., digestive juices. The toxic potential and the internalization of such nanoparticles by nontarget cells were also examined. The aim of this study was to provide experimental evidence on the formation of Co²⁺, Fe²⁺, and Fe³⁺ ions from CoFe₂O₄ nanoparticles in the digestive juices of a model organism. Standard toxicological parameters were assessed. Cell membrane stability was tested with a modified method for measurement of its quality. Proton-induced X-ray emission and low energy synchrotron radiation X-ray fluorescence were used to study internalization and distribution of Co and Fe. Co²⁺ ions were found to be more toxic than nanoparticles. We confirmed that Co²⁺ ions accumulate in the hepatopancreas, but Fe^<i>n</i>+ ions or CoFe₂O₄ nanoparticles are not retained in vivo. A model biological system with a terrestrial isopod is suited to studies of the potential dissolution of ions and other products from metal-containing nanoparticles in biologically complex media