In vivo-induced size transformation of cerium oxide nanoparticles in both lung and liver does not affect long-term hepatic accumulation following pulmonary exposure

Recent findings show that cerium oxide (CeO2) nanoparticles may undergo in vivo-induced size transformation with the formation of smaller particles that could result in a higher translocation following pulmonary exposure compared to virtually insoluble particles, like titanium dioxide (TiO2). Therefore, we compared liver deposition of CeO2 and TiO2 nanoparticles of similar primary sizes 1, 28 or 180 days after intratracheal instillation of 162 μg of NPs in female C57BL/6 mice. Mice exposed to 162 μg CeO2 or TiO2 nanoparticles by intravenous injection or oral gavage were included as reference groups to assess the amount of NPs that reach the liver bypassing the lungs and the translocation of NPs from the gastrointestinal tract to the liver, respectively. Pulmonary deposited CeO2 nanoparticles were detected in the liver 28 and 180 days post-exposure and TiO2 nanoparticles 180 days post-exposure as determined by darkfield imaging and by the quantification of Ce and Ti mass concentration by inductively coupled plasma-mass spectrometry (ICP-MS). Ce and Ti concentrations increased over time and 180 days post-exposure the translocation to the liver was 2.87 ± 3.37% and 1.24 ± 1.98% of the initial pulmonary dose, respectively. Single particle ICP-MS showed that the size of CeO2 nanoparticles in both lung and liver tissue decreased over time. No nanoparticles were detected in the liver following oral gavage. Our results suggest that pulmonary deposited CeO2 and TiO2 nanoparticles translocate to the liver with similar calculated translocation rates despite their different chemical composition and shape. The observed particle size distributions of CeO2 nanoparticles indicate in vivo processing over time both in lung and liver. The fact that no particles were detected in the liver following oral exposure showed that direct translocation of nanoparticles from lung to the systemic circulation was the most important route of translocation for pulmonary deposited particles.

近期研究表明，氧化铈（cerium oxide, CeO₂）纳米颗粒可能发生体内诱导的尺寸转变，形成更小的颗粒；与二氧化钛（titanium dioxide, TiO₂）等几乎不溶性颗粒相比，其经呼吸道暴露后的体内转运效率可能更高。为此，本研究选取雌性C57BL/6小鼠，经气管内滴注染毒162 μg纳米颗粒（nanoparticles, NPs）后，分别于1、28、180天检测两组原始尺寸相似的CeO₂与TiO₂纳米颗粒的肝脏沉积量。同时设置静脉注射染毒组与灌胃染毒组作为参考对照：静脉注射组用于评估绕过肺部直接抵达肝脏的纳米颗粒剂量，灌胃组则用于分析纳米颗粒从胃肠道向肝脏的转运情况。通过暗场显微成像（darkfield imaging）以及电感耦合等离子体质谱法（inductively coupled plasma-mass spectrometry, ICP-MS）定量检测Ce与Ti的质量浓度，结果显示：暴露后28天和180天即可在肝脏中检测到呼吸道沉积的CeO₂纳米颗粒，而TiO₂纳米颗粒仅在暴露后180天被检出。Ce与Ti的浓度随时间推移逐渐升高，暴露后180天，二者向肝脏的转运量分别占初始经呼吸道暴露剂量的2.87 ± 3.37%与1.24 ± 1.98%。单颗粒电感耦合等离子体质谱法（Single particle ICP-MS）检测发现，肺组织与肝脏组织中的CeO₂纳米颗粒尺寸均随时间推移逐渐减小。灌胃染毒组小鼠肝脏中未检测到任何纳米颗粒。本研究结果表明，尽管化学组成与形态存在差异，呼吸道沉积的CeO₂与TiO₂纳米颗粒向肝脏的转运率计算值并无显著差异。观测到的CeO₂纳米颗粒粒径分布特征提示，其在肺与肝脏组织中均存在随时间变化的体内转化过程。灌胃暴露后未在肝脏中检出颗粒这一结果证实，纳米颗粒从肺部直接进入体循环是呼吸道沉积颗粒体内转运的最主要途径。