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首页> 外文期刊>Journal of biochemical and molecular toxicology >In vivo immunotoxicity of Gd_2O_3:Eu~3+ nanoparticles and the associated molecular mechanism
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In vivo immunotoxicity of Gd_2O_3:Eu~3+ nanoparticles and the associated molecular mechanism

机译：Gd_2O_3的体内免疫毒性：Eu〜3 +纳米粒子和相关分子机制

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The in vivo toxicity of Gd_2O_3:Eu~3+ 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 Gd_2O_3:Eu~3+ 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 Gd_2O_3:Eu~3+ and gadodiamide, a commonly used contrast agent, were not significantly different, and the mice were able to tolerate the immunotoxicity caused Gd_2O_3:Eu~3+ NPs in vitro and in vivo experiments. The results suggest that Gd_2O_3:Eu~3+ NPs are sufficiently biocompatible to be used safely in pre-clinical applications and show promise as bio-imaging agents. Moreover, the in vivo molecular mechanism of immunotoxicity caused by the Gd_2O_3:Eu~3+ NPs provides a platform for further research on the immunotoxicity of nano-sized biomaterials.
机译：Gd_2O_3:Eu~3+纳米颗粒（NPs）作为用于分子成像的双模纳米探针的体内毒性尚未研究，相应的免疫毒性分子机制尚不清楚。在本研究中，我们研究了Gd_2O_3:Eu~3+NPs的细胞毒性、体外凋亡和体内免疫毒性。NPs对BALB/c小鼠的免疫毒性很小。我们探索了磷脂酰肌醇3-激酶（PI3K）信号通路的可能作用，发现活性氧物种可以作为细胞信号的二级信使，抑制肝脏中PI3K的表达。PI3K抑制引起的免疫抑制有助于小鼠适应应激。Gd_2O_3:Eu~3+和常用造影剂钆二酰胺引起的免疫毒性没有显著差异，小鼠能够耐受Gd_2O_3:Eu~3+NPs引起的免疫毒性。结果表明，Gd_2O_3:Eu~3+NPs具有足够的生物相容性，可安全用于临床前应用，并有望成为生物显像剂。此外，Gd_2O_3:Eu~3+NPs免疫毒性的体内分子机制为进一步研究纳米生物材料的免疫毒性提供了平台。

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