The physicochemical properties of nanoparticles (NPs) influence their biological outcomes. We assessed the effects of an amorphous silica coating on the pharmacokinetics and pulmonary effects of CeO2 NPs following intratracheal (IT) instillation, gavage and intravenous injection in rats. Uncoated and silica-coated CeO2 NPs were generated by flame spray pyrolysis and later neutron-activated. These radioactive NPs were IT-instilled, gavaged, or intravenously (IV) injected in rats. Animals were analyzed over 28 days post-IT, 7 days post-gavage and 2 days post-injection. Our data indicate that silica coating caused more but transient lung inflammation compared to uncoated CeO2. The transient inflammation of silica-coated CeO2 was accompanied by its enhanced clearance. Then, from 7 to 28 days, clearance was similar although significantly more 141Ce from silica-coated (35 %) was cleared than from uncoated (19 %) 141CeO2 in 28 days. The protein coronas of the two NPs were significantly different when they were incubated with alveolar lining fluid. Despite more rapid clearance from the lungs, the extrapulmonary 141Ce from silica-coated 141CeO2 was still minimal (<1 %) although lower than from uncoated 141CeO2 NPs. Post-gavage, nearly 100 % of both NPs were excreted in the feces consistent with very low gut absorption. Both IV-injected 141CeO2 NP types were primarily retained in the liver and spleen. The silica coating significantly altered the plasma protein corona composition and enhanced retention of 141Ce in other organs except the liver. We conclude that silica coating of nanoceria alters the biodistribution of cerium likely due to modifications in protein corona formation after IT and IV administration.

中文翻译：

---

二氧化硅涂层影响氧化铈纳米粒子的电晕和生物动力学。


纳米颗粒 (NP) 的理化性质影响其生物学结果。我们评估了无定形二氧化硅涂层对大鼠气管内 (IT) 滴注、强饲和静脉注射后 CeO2 纳米粒子的药代动力学和肺部影响的影响。未涂覆和二氧化硅涂覆的 CeO2 纳米粒子通过火焰喷射热解生成，然后中子激活。这些放射性纳米颗粒通过 IT 滴注、强饲或静脉 (IV) 注射到大鼠体内。在IT后28天、强饲后7天和注射后2天对动物进行分析。我们的数据表明，与未涂层的 CeO2 相比，二氧化硅涂层引起更多但短暂的肺部炎症。二氧化硅包覆的 CeO2 的短暂炎症伴随着其清除率的增强。然后，从 7 到 28 天，尽管 28 天内从二氧化硅涂层 (35%) 中清除的 141Ce 明显多于从未涂层 (19%) 141CeO2 中清除的情况，但清除情况相似。当两种纳米粒子与肺泡内壁液一起孵育时，其蛋白冠存在显着差异。尽管从肺部的清除速度更快，但来自二氧化硅涂层的 141CeO2 的肺外 141Ce 仍然很少（<1%），尽管低于来自未涂层的 141CeO2 NP。灌胃后，几乎 100% 的两种 NP 均通过粪便排出，这与肠道吸收率非常低相一致。两种静脉注射的 141CeO2 NP 类型主要保留在肝脏和脾脏中。二氧化硅涂层显着改变了血浆蛋白冠的组成，并增强了 141Ce 在除肝脏以外的其他器官中的保留。我们得出的结论是，纳米陶瓷的二氧化硅涂层改变了铈的生物分布，这可能是由于 IT 和 IV 给药后蛋白质冠形成的改变所致。