Journal
NATURE NANOTECHNOLOGY
Volume 16, Issue 6, Pages 708-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41565-021-00856-w
Keywords
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Funding
- National Key Research and Development Program of China [2016YFA0201600, 2020YFA0710700, 2016YFE0133100]
- Innovative Research Groups of the National Natural Science Foundation of China [11621505]
- National Natural Science Foundation of China [31971311, 2202780088]
- Program for International SAMP
- T Cooperation Projects of the Ministry of Science and Technology of China [2018YFE0117200]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB36000000]
- CAS Interdisciplinary Innovation Team
- Bureau of International Cooperation Chinese Academy of Sciences [GJHG1852]
- Research and Development Project in Key Areas of Guangdong Province [2019B090917011]
- Users with Excellence Project of Hefei Science Center CAS [2018HSC-UE004]
- SSRF [BL-15U1A, BL-14W1]
- BSRF [1W1B, 4B7A]
- Hefei Light Source of the National Synchrotron Radiation Laboratory [BL07W]
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Understanding the in vivo biotransformation of nanomaterials, such as molybdenum derived from MoS2, can shed light on their long-term effects on liver metabolism. Through a combination of in vivo experiments and molecular dynamics simulations, the study reveals that the biodistribution of molybdenum is mediated by protein coronas, mainly with apolipoprotein E, leading to increased enzyme activities in the liver. The findings suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules in organisms.
Understanding the in vivo biotransformation of nanomaterials used for biomedical applications might shed light on their long-term effects and safety. Here the authors show that molybdenum derived from nanomaterials is mainly transported in the liver, in a corona-mediated process, and is incorporated in molybdoenzymes, with an effect on liver metabolism. 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 MoS2 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 MoS2 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.
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