Fate of cerium dioxide nanoparticles in endothelial cells: exocytosis

Abstract

Although cytotoxicity and endocytosis of nanoparticles have been the subject of numerous studies, investigations regarding exocytosis as an important mechanism to reduce intracellular nanoparticle accumulation are rather rare and there is a distinct lack of knowledge. The current study investigated the behavior of human microvascular endothelial cells to exocytose cerium dioxide (CeO2) nanoparticles (18.8 nm) by utilization of specific inhibitors [brefeldin A; nocodazole; methyl-β-cyclodextrin (MβcD)] and different analytical methods (flow cytometry, transmission electron microscopy, inductively coupled plasma mass spectrometry). Overall, it was found that endothelial cells were able to release CeO2 nanoparticles via exocytosis after the migration of nanoparticle containing endosomes toward the plasma membrane. The exocytosis process occurred mainly by fusion of vesicular membranes with plasma membrane resulting in the discharge of vesicular content to extracellular environment. Nevertheless, it seems to be likely that nanoparticles present in the cytosol could leave the cells in a direct manner. MβcD treatment led to the strongest inhibition of the nanoparticle exocytosis indicating a significant role of the plasma membrane cholesterol content in the exocytosis process. Brefeldin A (inhibitor of Golgi-to-cell-surface-transport) caused a higher inhibitory effect on exocytosis than nocodazole (inhibitor of microtubules). Thus, the transfer from distal Golgi compartments to the cell surface influenced the exocytosis process of the CeO2 nanoparticles more than the microtubule-associated transport. In conclusion, endothelial cells, which came in contact with nanoparticles, e.g., after intravenously applied nano-based drugs, can regulate their intracellular nanoparticle amount, which is necessary to avoid adverse nanoparticle effects on cells.

Effects of cerium oxide nanoparticles on hemostasis: Coagulation, platelets, and vascular endothelial cells

“…As showed by TEM images, NC uptake in endothelial cells is dependent on the incubation time, increasing gradually with the incubation and occurring through clathrin‐mediated endocytosis, as showed in microvascular endothelial cells . After 3 h, NC are already incorporated in endothelial cells and, after 24 h, their uptake is total.…”

Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects

“…Among them are gallium nitride nanoparticles (GaN NPs) [97], cerium dioxide nanoparticles (CeO 2 NPs) [98], gold nanospheres [99,100], silica NPs [101][102][103], CdTe [104], and silver nanoparticles [105] to quote some examples. Silver nanoparticles have received much attention as of late due to the biological effects they produce in endothelial cells, e.g., decreased cell viability, induced apoptosis, increased ROS production, increased production of IL-6 and IL-8 interleukins, and increased expression of adhesion proteins, which can promote inflammation [106][107][108].…”

Cerium dioxide (CeO2) nanoparticles decrease arsenite (As(III)) cytotoxicity to 16HBE14o- human bronchial epithelial cells

“…A variety of widely used NPs (such as TiO 2 , silver and SiO 2 ) have been reported to cause lysosomal dysfunction, and subsequently lead to adverse effects on cells including cell death (Stern et al, 2012). Although numerous studies have been conducted to investigate the cytotoxicity of CeO 2 NPs, cytotoxic effects resulting from lysosomal NP accumulation has not been reported (Song et al, 2014; Stern et al, 2012; Strobel et al, 2015). In this work CeO 2 NP uptake by human bronchial epithelial cells was observed.…”