Rare earth oxide nanomaterials (REONs) hold considerable promise, with high availability and various potential applications in nanomedicine and other various fields. This results in potential REON exposure to humans and the environment through diverse routes and the potential adverse effects induced by biological application of these materials are becoming an increasing concern. This study investigates the cytotoxicity of REONs: nLa2O3, nEu2O3, nDy2O3 and nYb2O3, in macrophages. A significant difference was observed in the extent of cytotoxicity induced in macrophages by differential REONs, with the high-atomic number materials (i.e., nYb2O3) tending to be less toxic than low-atomic number materials (nLa2O3 and nEu2O3). Accumulation of REONs induced lysosomal membrane permeabilization, leading to the release of cathepsins and an elevation of intracellular and mitochondrial calcium. Increased calcium levels further enhanced the permeabilization of mitochondrial membranes, triggering cell death. The sequestration of phosphorus from lysosomal membranes was observed, as well as the release of dissolved rare earth metal ions, which contributed to overall REON cytotoxicity. Further mechanistic investigation established that autophagy was a fundamental cell death pathway and the blockage of autophagic flux by REONs, causing cells to be unable to clear damaged cellular components by fusion of lysosomes and autosomes, resulting in enhanced cell death. This detailed investigation of signaling pathways driving REON-induced toxicity to macrophages is essential for better understanding of their potential health risks to humans and the environment.

Toxicity of rare earth nanomaterials in macrophages

255th National Meeting (2018)

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