Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, People's Republic of China.
Int J Nanomedicine. 2011;6:2071-81. doi: 10.2147/IJN.S21657. Epub 2011 Sep 20.
Gold nanoparticle toxicity research is currently leading towards the in vivo experiment. Most toxicology data show that the surface chemistry and physical dimensions of gold nanoparticles play an important role in toxicity. Here, we present the in vivo toxicity of 5, 10, 30, and 60 nm PEG-coated gold nanoparticles in mice.
Animal survival, weight, hematology, morphology, organ index, and biochemistry were characterized at a concentration of 4000 μg/kg over 28 days.
The PEG-coated gold particles did not cause an obvious decrease in body weight or appreciable toxicity even after their breakdown in vivo. Biodistribution results show that 5 nm and 10 nm particles accumulated in the liver and that 30 nm particles accumulated in the spleen, while the 60 nm particles did not accumulate to an appreciable extent in either organ. Transmission electron microscopic observations showed that the 5, 10, 30, and 60 nm particles located in the blood and bone marrow cells, and that the 5 and 60 nm particles aggregated preferentially in the blood cells. The increase in spleen index and thymus index shows that the immune system can be affected by these small nanoparticles. The 10 nm gold particles induced an increase in white blood cells, while the 5 nm and 30 nm particles induced a decrease in white blood cells and red blood cells. The biochemistry results show that the 10 nm and 60 nm PEG-coated gold nanoparticles caused a significant increase in alanine transaminase and aspartate transaminase levels, indicating slight damage to the liver.
The toxicity of PEG-coated gold particles is complex, and it cannot be concluded that the smaller particles have greater toxicity. The toxicity of the 10 nm and 60 nm particles was obviously higher than that of the 5 nm and 30 nm particles. The metabolism of these particles and protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future.
金纳米颗粒毒性研究目前正朝着体内实验的方向发展。大多数毒理学数据表明,金纳米颗粒的表面化学性质和物理尺寸在毒性中起着重要作用。在这里,我们介绍了 5、10、30 和 60nm 的聚乙二醇(PEG)包覆金纳米颗粒在小鼠体内的毒性。
在 4000μg/kg 的浓度下,用 28 天的时间对动物的存活率、体重、血液学、形态学、器官指数和生物化学进行了描述。
PEG 包覆的金颗粒即使在体内破裂后,也不会导致明显的体重下降或明显的毒性。生物分布结果表明,5nm 和 10nm 颗粒在肝脏中积累,而 30nm 颗粒在脾脏中积累,而 60nm 颗粒在这两个器官中都没有显著积累。透射电子显微镜观察表明,5nm、10nm、30nm 和 60nm 颗粒位于血液和骨髓细胞中,5nm 和 60nm 颗粒优先在血细胞中聚集。脾脏指数和胸腺指数的增加表明,这些小纳米颗粒可以影响免疫系统。10nm 金颗粒诱导白细胞增加,而 5nm 和 30nm 颗粒导致白细胞和红细胞减少。生化结果表明,10nm 和 60nm PEG 包覆的金纳米颗粒导致丙氨酸转氨酶和天冬氨酸转氨酶水平显著升高,表明肝脏有轻微损伤。
PEG 包覆的金纳米颗粒的毒性是复杂的,不能得出较小的颗粒毒性更大的结论。10nm 和 60nm 颗粒的毒性明显高于 5nm 和 30nm 颗粒。这些颗粒的代谢和肝脏的保护将是金基纳米材料在未来医学应用中更重要的问题。