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

Abstract

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). In vitro and in vivo 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 (SiO 2 -SPIONs), which have a high potential in medicine, caused an increased cellular amount of acid organelles and phospholipids. In SiO 2 -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 SiO 2 -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 SiO 2 -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. ARTICLE HISTORY

The Influence of BuqiHuoxueTongluo Formula on Histopathology and Pulmonary Function Test in Bleomycin‐Induced Idiopathic Pulmonary Fibrosis in Rats

“…Meanwhile, we could conclude the surface tension of alveoli through the hysteresis of the P-V loop [ 34 ], which is influenced by the pulmonary surfactant [ 35 ]. It is a complicated phospholipid and protein complex synthesized and secreted by AECII [ 10 ] and packed in LBs [ 36 ]. It could maintain the surface tension [ 37 ], prevent the hyperinflation and collapse of alveoli, and hold a stable alveoli space.…”

In Vitro Cytotoxicity Evaluation of the Magnéli Phase Titanium Suboxides (TixO2x−1) on A549 Human Lung Cells

“…Lysosomal overloading with indigestible substances like NPs may lead to severe degenerative alterations of the cells. This indicates that supposedly inert but biopersistent nanomaterials can be harmful by interfering with normal endo-lysosomal functioning [9]. Lysosomal destabilization has already been shown as a cytotoxicity mechanism of TiO 2 NPs in human bronchial epithelial cells and in murine fibroblast cells [47,48].…”

“…This leads to versatile NP-cell interactions and a variety of cellular responses [1]. Numerous investigations have already been conducted that studied cell interactions with various types of NPs, from polymeric NPs [2], lipid-based NPs [3], carbon based NPs [4,5,6], and metal oxide NPs [7,8,9]. Nevertheless, numerous NPs with modified or new properties are being developed every day, and understanding their interactions with cells and cellular responses is an important scientific issue that has to be addressed in order to assure their safe and efficient use [10].…”

“…The toxicity of NPs is most frequently attributed to oxidative stress, leading to the damage of biomolecules and cell organelles. NPs that come into contact with cells can be endocytosed, entering endo-lysosomal compartments of the cells, which can lead to lysosomal dysfunction with potential functional consequences [9,27]. Toxicity of NPs is often accompanied by the perturbation of intracellular Ca 2+ homeostasis, which is associated with energetic and metabolic imbalance and other cellular dysfunctions [26,28,29].…”

Iron oxide nanoparticle-induced hematopoietic and immunological response in rats

“…2 A number of studies have described the acute toxicity of the IONPs in animals. [6][7][8][9] while other studies reported no apparent signs of toxicity. 3,9,10 Understanding the toxicological proles of IONPs, a transition metal is vital to ensure that the products are safe and developed with maximum benets and minimal risks.…”