Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO₂ nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more in C57BL/6 mice. Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. Light microscopy revealed greater liver vacuolation in C57BL/6 mice and a nanoceria-induced decrease in BALB/c but not C57BL/6 mice vacuolation. Nanoceria increased spleen lymphoid white pulp cell density in BALB/c but not C57BL/6 mice. Electron microscopy showed intracellular nanoceria particles bioprocessed to form crystalline cerium phosphate nanoneedles. Ferritin accumulation was greatly increased proximal to the nanoceria, forming core-shell-like structures in C57BL/6 but even distribution in BALB/c mice. Conclusions: BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. Nanoceria uptake, initiation of bioprocessing, and crystalline cerium phosphate nanoneedle formation were rapid. Ferritin greatly increased with a macrophage phenotype-dependent distribution. Further study will be needed to understand the mechanisms underlying the observed differences.

先前的研究表明，C57BL/6 与 BALB/c 小鼠的纳米颗粒清除率不同，分别易于发生 Th1 和 Th2 免疫反应的菌株。目的：评估纳米氧化铈（氧化铈，CeO ₂纳米颗粒）摄取时间过程和器官分布、细胞和氧化应激以及生物加工作为小鼠品系的函数。方法：C57BL/6 和 BALB/c 雌性小鼠腹腔注射 10 mg/kg 纳米氧化铈或载体，0.5 至 24 小时后终止。收集器官用于铈分析；具有元素映射的光学和电子显微镜；和蛋白质羰基、IL-1β 和 caspase-1 测定。结果：外周器官铈显着增加，通常在 C57BL/6 小鼠中更多。6 小时时，肝脏中的 Caspase-1 显着升高，在 BALB/c 小鼠中升高幅度更大，表明炎症小体途径激活。光学显微镜显示 C57BL/6 小鼠肝脏空泡化程度更高，纳米氧化铈诱导的 BALB/c 降低，但 C57BL/6 小鼠空泡化没有。Nanoceria 增加了 BALB/c 而非 C57BL/6 小鼠的脾淋巴样白髓细胞密度。电子显微镜显示细胞内纳米氧化铈颗粒经过生物处理形成结晶磷酸铈纳米针。铁蛋白积累在纳米氧化铈附近大大增加，在 C57BL/6 中形成核壳状结构，但在 BALB/c 小鼠中分布均匀。结论：BALB/c 小鼠对纳米氧化铈诱导的效应更敏感，例如肝 caspase-1 激活、肝空泡化减少和脾细胞密度增加。纳米氧化铈的吸收、生物加工的启动和结晶磷酸铈纳米针的形成是迅速的。铁蛋白显着增加，呈巨噬细胞表型依赖性分布。需要进一步研究以了解所观察到的差异背后的机制。