Nanoparticles with biomedical applications should be evaluated for their biocompatibility. Rare-earth doped nanoparticles with unique spectral properties are superior in vivo optical probes in comparison with quantum dots and organic dyes, however, studies describing their nano-bio interactions are still limited. Here, we have evaluated the nano-bio interactions of green-synthesized, phase-pure BaF₂ nanoparticles doped with rare-earth (RE³⁺ = Ce³⁺/Tb³⁺) ions using larval zebrafish. We found that zebrafish can tolerate a wide concentration range of these nanoparticles, as the maximal lethality was observed at very high concentrations (more than 200 mg L⁻¹) upon five days of continuous exposure. At a concentration of 10 mg L⁻¹, at which Zn²⁺, Ti⁴⁺ and Ag⁺ nanoparticles are reported to be lethal to developing zebrafish, continuous exposure to our nanoparticles for four days produced no developmental anomalies, craniofacial defects, cardiac toxicity or behavioural abnormalities in the developing zebrafish larvae. We have also found that the doping of rare-earth ions has no major effect on these biomarkers. Interestingly, the function of acetylcholinesterase (AChE) and the cellular metabolic activity of whole zebrafish larvae remained unchanged, even during continuous exposure to these nanoparticles at 150 mg L⁻¹ for four days; however, severe developmental toxicities were evident at this high concentration. Based on these results, we can conclude that the biocompatibility of rare-earth doped nanoparticles is concentration dependent. Not all biomarkers are sensitive to these nanoparticles. The high concentration-dependent toxicity occurs through a mechanism distinct from changes in the metabolic or AChE activity. The significance of these findings lies in using these nanoparticles for bioimaging applications and biomarker studies, especially for prolonged exposure times.

中文翻译：

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稀土掺杂的BaF2纳米磷光体的纳米生物相互作用塑造了斑马鱼的发育过程。

具有生物医学应用的纳米颗粒应评估其生物相容性。与量子点和有机染料相比，具有独特光谱特性的稀土掺杂纳米粒子在体内光学探针方面表现优异，但是，描述其纳米生物相互作用的研究仍然有限。在这里，我们使用幼虫斑马鱼评估了掺有稀土（RE ³⁺ = Ce ³⁺ / Tb ³⁺）离子的绿色合成，纯相BaF ₂纳米颗粒的纳米生物相互作用。我们发现斑马鱼可以耐受这些纳米颗粒的宽浓度范围，因为在非常高的浓度（大于200 mg L ^-1时观察到最大杀伤力））连续暴露五天。据报道，在浓度为10 mg L ^-1的情况下，Zn 2 ⁺，Ti ⁴⁺和Ag ⁺纳米颗粒对发育中的斑马鱼具有致死性，连续暴露四天对我们的纳米颗粒没有造成发育异常，颅面缺陷，心脏毒性或发育中的斑马鱼幼虫的行为异常。我们还发现，掺杂稀土离子对这些生物标志物没有重大影响。有趣的是，即使在连续暴露于150 mg L ^-1的纳米颗粒期间，乙酰胆碱酯酶（AChE）的功能和整个斑马鱼幼虫的细胞代谢活性也保持不变。四天；然而，在这种高浓度下，明显的严重的发育毒性。基于这些结果，我们可以得出结论，稀土掺杂纳米颗粒的生物相容性是浓度依赖性的。并非所有生物标志物都对这些纳米颗粒敏感。高浓度依赖性毒性是通过不同于代谢或AChE活性变化的机制发生的。这些发现的意义在于将这些纳米颗粒用于生物成像应用和生物标志物研究，尤其是延长曝光时间。