Cytotoxicity and hemolysis of rare earth ions and nanoscale/bulk oxides (La, Gd, and Yb): Interaction with lipid membranes and protein corona formation

The widespread application of rare earth elements (REEs) has raised concerns about their potential release into the environment and subsequent ingestion by humans. Therefore, it is essential to evaluate the cytotoxicity of REEs. Here, we investigated the interactions between three typical REEs (La, Gd, and Yb) ions as well as their nanometer/μm-sized oxides and red blood cells (RBCs), a plausible contact target for nanoparticles when they enter the bloodstream. Hemolysis of REEs at 50–2000 μmol L−1 was examined to simulate their cytotoxicity under medical or occupational exposure. We found that the hemolysis due to the exposure of REEs was highly dependent on their concentration, and the cytotoxicity followed the order of La3+ > Gd3+ > Yb3+. The cytotoxicity of REE ions (REIs) is higher than REE oxides (REOs), while nanometer-sized REO caused more hemolysis than that μm-sized REO. The production of reactive oxygen species (ROS), ROS quenching experiment, as well as the detection of lipid peroxidation, confirmed that REEs causes cell membrane rupture by ROS-related chemical oxidation. In addition, we found that the formation of a protein corona on REEs increased the steric repulsion between REEs and cell membranes, hence mitigating the cytotoxicity of REEs. The theoretical simulation indicated the favorable interaction of REEs with phospholipids and proteins. Therefore, our findings provide a mechanistic explanation for the cytotoxicity of REEs to RBCs once they have entered the blood circulation system of organisms.