China National Center for Food Safety Risk Assessment, Beijing 100022, People's Republic of China.
Key Laboratory of Animal Epidemiology of Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.
Int J Nanomedicine. 2019 Jul 16;14:5175-5186. doi: 10.2147/IJN.S197565. eCollection 2019.
As a promising nanomaterial for biomedical applications, zirconia nanoparticles (ZrO) have aroused concern recently, but the toxicity of ZrO in vivo has received little attention. The aim of this study is to demonstrate the systematic single dose toxicity, biodistribution and oxidative damage of ZrO in vivo after intravenous injection in mice. Ten ICR mice were used at the high dose of ZrO including 600, 500, 400 and 300mg/kg. Maximum tolerated dose (MTD) of 150 nm ZrO was determined as 500mg/kg. Hematology analysis and blood biochemical assay were determined for the evaluation of oxidative damage caused by ZrO. Biodistribution of ZrO was investigated by ICP-OES and TEM. Mice treated with higher dose (500mg/kg) showed significant spread in white blood cell counts (<0.05). Especially, the serum ALT levels of 500mg/kg groups increased significantly (<0.05) compared with the control group. ZrO particles would not induce any changes in appearance and micromorphology of liver at 100 and 350mg/kg. Spleen samples showed no significant changes in micromorphology of the lymphoid follicles and in the size of the red pulp after injection of ZrO at all doses. The serum of ZrO-treated animals (350 and 500mg/kg) has reduced levels of SOD compared to the control group (<0.05). ZrO persists in membrane-enclosed vesicles called lysosomes in the liver and spleen macrophages without abnormal changes of ultrastructure. These findings would contribute to the future development of ZrO-based drug delivery system and other biomedical applications.
作为一种有前途的生物医学应用纳米材料，氧化锆纳米颗粒（ZrO）最近引起了关注，但体内 ZrO 的毒性尚未得到重视。本研究旨在展示静脉注射后 ZrO 在体内的系统单次剂量毒性、生物分布和氧化损伤。10 只 ICR 小鼠分别接受高剂量 ZrO（包括 600、500、400 和 300mg/kg）处理。确定 150nm ZrO 的最大耐受剂量（MTD）为 500mg/kg。通过 ICP-OES 和 TEM 研究 ZrO 的生物分布。用更高剂量（500mg/kg）处理的小鼠白细胞计数明显增加（<0.05）。特别是，500mg/kg 组的血清 ALT 水平与对照组相比显著升高（<0.05）。100 和 350mg/kg 剂量的 ZrO 不会引起肝脏外观和微形态的任何变化。脾脏样本在注射 ZrO 后，在淋巴滤泡的微形态和红髓的大小方面均无明显变化。与对照组相比，ZrO 处理动物（350 和 500mg/kg）的血清 SOD 水平降低（<0.05）。ZrO 在肝脏和脾脏巨噬细胞中的溶酶体等膜封闭小泡中持续存在，超微结构无异常变化。这些发现将有助于未来基于 ZrO 的药物输送系统和其他生物医学应用的发展。
