Y₂O₃ Nanoparticles Caused Bone Tissue Damage by Breaking the Intracellular Phosphate Balance in Bone Marrow Stromal Cells

Y₂O₃ nanoparticles (NPs) have become great promising products for numerous applications in nanoscience especially for biomedical application, therefore increasing the probability of human exposure and gaining wide attention in biosecurity. It is well known that rare earth (RE) materials are deposited in the bone and excreted very slowly. Nevertheless, the effect of Y₂O₃-based NPs on bone metabolism has not been exactly known yet. In the present study, the effects of Y₂O₃ NPs on bone marrow stromal cells (BMSCs) and bone metabolism in mice after intravenous injection were studied. The results demonstrated that Y₂O₃ NPs could be taken up into BMSCs and localized in acidifying intracellular lysosomes and underwent dissolution and transformation from Y₂O₃ to YPO₄, which could lead to a break in the intracellular phosphate balance and induce lysosomal- and mitochondrial-dependent apoptosis pathways. Furthermore, after being administered to mice, a higher concentration of yttrium occurred in bone, which caused the apoptosis of bone cells and induced the destruction of bone structure. However, the formation of a YPO₄ coating on the surface of Y₂O₃ NPs by pretreatment of Y₂O₃ NPs in lysosome-simulated body fluid could observably decrease the toxicity in vivo and in vitro. This study may be useful for practical application of Y₂O₃ NPs in the biomedical field.