CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China.
Sino-Danish Center for Education and Research, University of Chinese Academy of Sciences, Beijing, China.
Nat Nanotechnol. 2021 Jun;16(6):708-716. doi: 10.1038/s41565-021-00856-w. Epub 2021 Feb 18.
Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport-transformation-bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism.
由于对体内行为基本原理的理解不足，许多纳米级生物材料未能进入临床试验阶段。在这里，我们通过体内实验和分子动力学模拟相结合的方式，描述了 MoS 纳米材料的传输、转化和生物利用。我们发现，静脉注射后，钼在肝窦和脾红髓中明显富集。这种分布是由血液中自发形成的蛋白质冠介导的，主要与载脂蛋白 E 结合。MoS 的生物转化导致钼掺入钼酶中，从而增加了钼在肝脏中的特异性活性，影响了其代谢。我们的研究结果表明，纳米材料在体内经历了一个由蛋白质冠桥接的传输-转化-生物利用链，并表明由必需微量元素组成的纳米材料可能被转化为生物体可以利用的活性生物分子。我们的研究结果还表明，纳米材料的长期生物转化可能会对肝脏代谢产生影响。
