In vivo immunotoxicity of Gd₂ O₃ :Eu³⁺ nanoparticles and the associated molecular mechanism

The in vivo toxicity of Gd₂ O₃ :Eu³⁺ nanoparticles (NPs) used as dual-modal nanoprobes for molecular imaging has not been studied, and the corresponding molecular mechanism of immunotoxicity remains unknown. In this study, we investigated the cytotoxicity, in vitro apoptosis, and in vivo immunotoxicity of Gd₂ O₃ :Eu³⁺ NPs. The NPs showed little immunotoxicity to BALB/c mice. We explored the possible role of the phosphoinositide 3-kinase (PI3K) signaling pathway and found that reactive oxygen species could act as secondary messengers in cellular signaling, inhibiting PI3K expression in the liver. The immune suppression caused by PI3K inhibition helped the mice adapt to stress. The immunotoxicities caused by Gd₂ O₃ :Eu³⁺ and gadodiamide, a commonly used contrast agent, were not significantly different, and the mice were able to tolerate the immunotoxicity caused Gd₂ O₃ :Eu³⁺ NPs in vitro and in vivo experiments. The results suggest that Gd₂ O₃ :Eu³⁺ NPs are sufficiently biocompatible to be used safely in preclinical applications and show promise as bio-imaging agents. Moreover, the in vivo molecular mechanism of immunotoxicity caused by the Gd₂ O₃ :Eu³⁺ NPs provides a platform for further research on the immunotoxicity of nano-sized biomaterials.