journal article·2021-06

Molybdenum derived from nanomaterials incorporates into molybdenum enzymes and affects their activities in vivo

Mingjing Cao, Rong Cai, Lina Zhao, Mengyu Guo, Liming Wang, Yucai Wang, Lili Zhang, Xiaofeng Wang, Haodong Yao, Chunyu Xie, Yalin Cong, Yong Guan, Xiayu Tao, Yaling Wang, Shaoxin Xu, Ying Liu, Yuliang Zhao, Chunying Chen

Nature Nanotechnology· Volume 16· Issue 6
Publisher page

Abstract

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.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Iron Metabolism and Disorders · Nanocluster Synthesis and Applications · Metalloenzymes and iron-sulfur proteins

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (52)

Show source-provided references
1. Manzeli, S., Ovchinnikov, D., Pasquier, D., Yazyev, O. V. & Kis, A. 2D transition metal dichalcogenides. Nat. Rev. Mater. 2, 17033 (2017).10.1038/natrevmats.2017.33 ↗
2. Yadav, V., Roy, S., Singh, P., Khan, Z. & Jaiswal, A. 2D MoS2‐based nanomaterials for therapeutic, bioimaging, and biosensing applications. Small 15, 1803706 (2019).10.1002/smll.201803706 ↗
3. Chen, Y., Tan, C., Zhang, H. & Wang, L. Two-dimensional graphene analogues for biomedical applications. Chem. Soc. Rev. 44, 2681–2701 (2015).10.1039/C4CS00300D ↗
4. Li, B. L. et al. Directing assembly and disassembly of 2D MoS2 nanosheets with DNA for drug delivery. ACS Appl. Mater. Interfaces 9, 15286–15296 (2017).10.1021/acsami.7b02529 ↗
5. Liu, T. et al. Drug delivery with pegylated MoS2 nano‐sheets for combined photothermal and chemotherapy of cancer. Adv. Mater. 26, 3433–3440 (2014).10.1002/adma.201305256 ↗
6. Yin, W. et al. High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy. ACS Nano 8, 6922–6933 (2014).10.1021/nn501647j ↗
7. Cheng, L. et al. Pegylated WS2 nanosheets as a multifunctional theranostic agent for in vivo dual-modal CT/photoacoustic imaging guided photothermal therapy. Adv. Mater. 26, 1886–1893 (2014).10.1002/adma.201304497 ↗
8. Xi, Q. et al. Highly sensitive and selective strategy for microRNA detection based on WS2 nanosheet mediated fluorescence quenching and duplex-specific nuclease signal amplification. Anal. Chem. 86, 1361–1365 (2014).10.1021/ac403944c ↗
9. Sarkar, D. et al. MoS2 field-effect transistor for next-generation label-free biosensors. ACS Nano 8, 3992–4003 (2014).10.1021/nn5009148 ↗
10. Wang, Z. et al. Chemical dissolution pathways of MoS2 nanosheets in biological and environmental media. Environ. Sci. Technol. 50, 7208–7217 (2016).10.1021/acs.est.6b01881 ↗
11. Kurapati, R. et al. Enzymatic biodegradability of pristine and functionalized transition metal dichalcogenide MoS2 nanosheets. Adv. Funct. Mater. 27, 1605176 (2017).10.1002/adfm.201605176 ↗
12. Hao, J. et al. In vivo long-term biodistribution, excretion, and toxicology of PEGylated transition-metal dichalcogenides MS2 (M = Mo, W, Ti) nanosheets. Adv. Sci. 4, 1600160 (2017).10.1002/advs.201600160 ↗
13. Schwarz, G., Mendel, R. R. & Ribbe, M. W. Molybdenum cofactors, enzymes and pathways. Nature 460, 839 (2009).10.1038/nature08302 ↗
14. Tenzer, S. et al. Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat. Nanotech. 8, 772–781 (2013).10.1038/nnano.2013.181 ↗
15. Boukhicha, M., Calandra, M., Measson, M.-A., Lancry, O. & Shukla, A. Anharmonic phonons in few-layer MoS2: Raman spectroscopy of ultralow energy compression and shear modes. Phys. Rev. B 87, 195316 (2013).10.1103/PhysRevB.87.195316 ↗
16. Pertoft, H. Fractionation of cells and subcellular particles with Percoll. J. Biochem. Biophy. Meth. 44, 1–30 (2000).10.1016/S0165-022X(00)00066-X ↗
17. Anderson, D. C., Mace, M. L., Brinkley, B. R., Martin, R. R. & Smith, C. W. Recurrent infection in glycogenosis type Ib: abnormal neutrophil motility related to impaired redistribution of adhesion sites. J. Infect. Dis. 143, 447–459 (1981).10.1093/infdis/143.3.447 ↗
18. Almeida, M. C. D., Silva, A. C., Barral, A. & Barral Netto, M. A simple method for human peripheral blood monocyte isolation. Mem. Inst. Oswaldo Cruz 95, 221–223 (2000).10.1590/S0074-02762000000200014 ↗
19. Parker, L. C., Whyte, M. K. B., Dower, S. K. & Sabroe, I. The expression and roles of Toll-like receptors in the biology of the human neutrophil. J. Leukoc. Biol. 77, 886–892 (2005).10.1189/jlb.1104636 ↗
20. Lunov, O. et al. Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line. ACS Nano 5, 1657–1669 (2011).10.1021/nn2000756 ↗
21. Monopoli, M. P., Åberg, C., Salvati, A. & Dawson, K. A. Biomolecular coronas provide the biological identity of nanosized materials. Nat. Nanotech. 7, 779–786 (2012).10.1038/nnano.2012.207 ↗
22. Yang, S. T., Liu, Y., Wang, Y. W. & Cao, A. Biosafety and bioapplication of nanomaterials by designing protein–nanoparticle interactions. Small 9, 1635–1653 (2013).10.1002/smll.201201492 ↗
23. Schoettler, S. et al. Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers. Nat. Nanotech. 11, 372–377 (2016).10.1038/nnano.2015.330 ↗
24. Bertrand, N. et al. Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nat. Commun. 8, 777 (2017).10.1038/s41467-017-00600-w ↗
25. Cai, R. & Chen, C. The crown and the scepter: roles of the protein corona in nanomedicine. Adv. Mater. 1805740, 1–13 (2018).
26. Floyd, C. N. & Ferro, A. The platelet fibrinogen receptor: from megakaryocyte to the mortuary. J. R. Soc. Med. Cardiovasc. Dis. 1, 1–13 (2012).10.5812/cardiovascmed.5417 ↗
27. Murao, K. et al. Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes. J. Biol. Chem. 272, 17551–17557 (1997).10.1074/jbc.272.28.17551 ↗
28. Shibuya, A. et al. Fcα/μ receptor mediates endocytosis of IgM-coated microbes. Nat. Immunol. 1, 441–446 (2000).10.1038/80886 ↗
29. Ross, G. D. & Lambris, J. Identification of a C3bi-specific membrane complement receptor that is expressed on lymphocytes, monocytes, neutrophils, and erythrocytes. J. Exp. Med. 155, 96–110 (1982).10.1084/jem.155.1.96 ↗
30. Qu, Y. et al. Full assessment of fate and physiological behavior of quantum dots utilizing Caenorhabditis elegans as a model organism. Nano Lett. 11, 3174–3183 (2011).10.1021/nl201391e ↗
31. Gouaux, E. & MacKinnon, R. Principles of selective ion transport in channels and pumps. Science 310, 1461–1465 (2005).10.1126/science.1113666 ↗
32. Cai, R. et al. Corona of thorns: the surface chemistry-mediated protein corona perturbs the recognition and immune response of macrophages. ACS Appl. Mater. Interfaces 12, 1997–2008 (2020).10.1021/acsami.9b15910 ↗
33. Monteiro, R. C., Kubagawa, H. & Cooper, M. Cellular distribution, regulation, and biochemical nature of an Fc alpha receptor in humans. J. Exp. Med. 171, 597–613 (1990).10.1084/jem.171.3.597 ↗
34. Suits, A. G., Chait, A., Aviram, M. & Heinecke, J. W. Phagocytosis of aggregated lipoprotein by macrophages: low density lipoprotein receptor-dependent foam-cell formation. Proc. Natl Acad. Sci. USA 86, 2713–2717 (1989).10.1073/pnas.86.8.2713 ↗
35. Chen, C., Li, Y.-F., Qu, Y., Chai, Z. & Zhao, Y. Advanced nuclear analytical and related techniques for the growing challenges in nanotoxicology. Chem. Soc. Rev. 42, 8266–8303 (2013).10.1039/c3cs60111k ↗
36. Wang, L. et al. Use of synchrotron radiation-analytical techniques to reveal chemical origin of silver-nanoparticle cytotoxicity. ACS Nano 9, 6532–6547 (2015).10.1021/acsnano.5b02483 ↗
37. Hille, R. Molybdenum and tungsten in biology. Trends Biochem. Sci. 27, 360–367 (2002).10.1016/S0968-0004(02)02107-2 ↗
38. Hille, R., Nishino, T. & Bittner, F. Molybdenum enzymes in higher organisms. Coord. Chem. Rev. 255, 1179–1205 (2011).10.1016/j.ccr.2010.11.034 ↗
39. Swinney, R., Hsu, S. & Tomlinson, G. Phase I and phase II enzyme polymorphisms and childhood cancer. J. Investig. Med. 54, 303–320 (2006).10.2310/6650.2006.05062 ↗
40. Sweeney, B. P. & Bromilow, J. Liver enzyme induction and inhibition: implications for anaesthesia. Anaesthesia 61, 159–177 (2006).10.1111/j.1365-2044.2005.04462.x ↗
41. Mota, C. et al. Critical overview on the structure and metabolism of human aldehyde oxidase and its role in pharmacokinetics. Coord. Chem. Rev. 368, 35–59 (2018).10.1016/j.ccr.2018.04.006 ↗
42. Li, H., Cui, H., Kundu, T. K., Alzawahra, W. & Zweier, J. L. Nitric oxide production from nitrite occurs primarily in tissues not in the blood: critical role of xanthine oxidase and aldehyde oxidase. J. Biol. Chem. 283, 17855–17863 (2008).10.1074/jbc.M801785200 ↗
43. Hille, R., Hall, J. & Basu, P. The mononuclear molybdenum enzymes. Chem. Rev. 114, 3963–4038 (2014).10.1021/cr400443z ↗
44. Cao, M., Li, J., Tang, J., Chen, C. & Zhao, Y. Gold nanomaterials in consumer cosmetics nanoproducts: analyses, characterization, and dermal safety assessment. Small 12, 5488–5496 (2016).10.1002/smll.201601574 ↗
45. Ren, J. et al. Precision nanomedicine development based on specific opsonization of human cancer patient-personalized protein coronas. Nano Lett. 19, 4692–4701 (2019).10.1021/acs.nanolett.9b01774 ↗
46. Elci, S. G. et al. Surface charge controls the suborgan biodistributions of gold nanoparticles. ACS Nano 10, 5536–5542 (2016).10.1021/acsnano.6b02086 ↗
47. Apenova, N., Peng, H., Hecker, M. & Brinkmann, M. A rapid and sensitive fluorometric method for determination of aldehyde oxidase activity. Toxicol. Appl. Pharm. 341, 30–37 (2018).10.1016/j.taap.2018.01.006 ↗
48. Kollman, J. M., Pandi, L., Sawaya, M. R., Riley, M. & Doolittle, R. F. Crystal structure of human fibrinogen. Biochemistry 48, 3877–3886 (2009).10.1021/bi802205g ↗
49. Sugio, S., Kashima, A., Mochizuki, S., Noda, M. & Kobayashi, K. Crystal structure of human serum albumin at 2.5 Å resolution. Protein Eng. 12, 439–446 (1999).10.1093/protein/12.6.439 ↗
50. Hatters, D. M., Peters-Libeu, C. A. & Weisgraber, K. H. Engineering conformational destabilization into mouse apolipoprotein E. A model for a unique property of human apolipoprotein E4. J. Biol. Chem. 280, 26477–26482 (2005).10.1074/jbc.M503910200 ↗
51. Nagar, B., Jones, R. G., Diefenbach, R. J., Isenman, D. E. & Rini, J. M. X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2. Science 280, 1277–1281 (1998).10.1126/science.280.5367.1277 ↗
52. Li, Y. X. et al. Structural insights into immunoglobulin M. Science 367, 1014–1017 (2020).10.1126/science.aaz5425 ↗