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Nano Research 2019, 12(4): 863-868 https://doi.org/10.1007/s12274-019-2313-z
Research Article | Issue | Published: 05 March 2019

Bioengineered magnetoferritin nanozymes for pathological identification of high-risk and ruptured atherosclerotic plaques in humans

Show Author's Information Tao Wang1,§,  Jiuyang He2,3,§,  Demin Duan3,  Bing Jiang3,  Peixia Wang3,  Kelong Fan3,  Minmin Liang3( ),  Xiyun Yan3( )
Department of Neurosurgery,Peking University Third Hospital,Beijing,100191,China;
Savaid Medical School,University of Chinese Academy of Sciences,Beijing,100049,China;
Key Laboratory of Protein and Peptide Pharmaceutical,Institute of Biophysics, Chinese Academy of Sciences,Beijing,100101,China;

§ Tao Wang and Jiuyang He contributed equally to this work.

Keywords:
nanozymes, atherosclerosis, high-risk plaques, ruptured plaques, magnetoferritin nanoparticles, pathological diagnosis
Topics:
DiagnosisEnzymesMacrophagesNanoparticles
Cite this article:
Wang T, He J, Duan D, et al. Bioengineered magnetoferritin nanozymes for pathological identification of high-risk and ruptured atherosclerotic plaques in humans. Nano Research, 2019, 12(4): 863-868. https://doi.org/10.1007/s12274-019-2313-z
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Abstract Full text About this article

Atherosclerotic plaque rupture results in thrombus formation and vessel occlusion, and is the leading cause of death worldwide. There is a pressing need to identify plaque vulnerability for the treatment of carotid and coronary artery diseases. Nanomaterials with enzyme-like properties have attracted significant interest by providing biological, diagnostic and prognostic information about the diseases. Here we showed that bioengineered magnetoferritin nanoparticles (M-HFn NPs) functionally mimic peroxidase enzyme and can intrinsically recognize plaque-infiltrated active macrophages, which drive atherosclerotic plaque progression and rupture and are significantly associated with the plaque vulnerability. The M-HFn nanozymes catalyze the oxidation of colorimetric substrates to give a color reaction that visualizes the recognized active macrophages for one-step pathological identification of plaque vulnerability. We examined 50 carotid endarterectomy specimens from patients with symptomatic carotid disease and demonstrated that the M-HFn nanozymes could distinguish active macrophage infiltration in ruptured and high-risk plaque tissues, and M-HFn staining displayed a significant correlation with plaque vulnerability (r = 0.89, P < 0.0001).


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About this article

Bioengineered magnetoferritin nanozymes for pathological identification of high-risk and ruptured atherosclerotic plaques in humans

Show Author's information Tao Wang1,§, Jiuyang He2,3,§, Demin Duan3, Bing Jiang3, Peixia Wang3, Kelong Fan3, Minmin Liang3( ), Xiyun Yan3( )
Department of Neurosurgery,Peking University Third Hospital,Beijing,100191,China;
Savaid Medical School,University of Chinese Academy of Sciences,Beijing,100049,China;
Key Laboratory of Protein and Peptide Pharmaceutical,Institute of Biophysics, Chinese Academy of Sciences,Beijing,100101,China;

§ Tao Wang and Jiuyang He contributed equally to this work.

Abstract

Atherosclerotic plaque rupture results in thrombus formation and vessel occlusion, and is the leading cause of death worldwide. There is a pressing need to identify plaque vulnerability for the treatment of carotid and coronary artery diseases. Nanomaterials with enzyme-like properties have attracted significant interest by providing biological, diagnostic and prognostic information about the diseases. Here we showed that bioengineered magnetoferritin nanoparticles (M-HFn NPs) functionally mimic peroxidase enzyme and can intrinsically recognize plaque-infiltrated active macrophages, which drive atherosclerotic plaque progression and rupture and are significantly associated with the plaque vulnerability. The M-HFn nanozymes catalyze the oxidation of colorimetric substrates to give a color reaction that visualizes the recognized active macrophages for one-step pathological identification of plaque vulnerability. We examined 50 carotid endarterectomy specimens from patients with symptomatic carotid disease and demonstrated that the M-HFn nanozymes could distinguish active macrophage infiltration in ruptured and high-risk plaque tissues, and M-HFn staining displayed a significant correlation with plaque vulnerability (r = 0.89, P < 0.0001).

Keywords: nanozymes, atherosclerosis, high-risk plaques, ruptured plaques, magnetoferritin nanoparticles, pathological diagnosis

References(38)

1

Otsuka, F.; Kramer, M. C. A.; Woudstra, P.; Yahagi, K.; Ladich, E.; Finn, A. V.; de Winter, R. J.; Kolodgie, F. D.; Wight, T. N.; Davis, H. R. et al. Natural progression of atherosclerosis from pathologic intimal thickening to late fibroatheroma in human coronary arteries: A pathology study. Atherosclerosis 2015, 241, 772–782.
DOI Google Scholar
2

Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease. New Engl. J. Med. 2005, 352, 1685–1695.
DOI Google Scholar
3

Narula, J.; Nakano, M.; Virmani, R.; Kolodgie, F. D.; Petersen, R.; Newcomb, R.; Malik, S.; Fuster, V.; Finn, A. V. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J. Am. Coll. Cardiol. 2013, 61, 1041–1051.
DOI Google Scholar
4

Virmani, R.; Kolodgie, F. D.; Burke, A. P.; Farb, A.; Schwartz, S. M. Lessons from sudden coronary death: A comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 2000, 20, 1262–1275.
DOI Google Scholar
5

Libby, P.; Ridker, P. M.; Maseri, A. Inflammation and atherosclerosis. Circulation 2002, 105, 1135–1143.
DOI Google Scholar
6

Moore, K. J.; Sheedy, F. J.; Fisher, E. A. Macrophages in atherosclerosis: A dynamic balance. Nat. Rev. Immunol. 2013, 13, 709–721.
DOI Google Scholar
7

Libby, P. Inflammation in atherosclerosis. Nature 2002, 420, 868–874.
DOI Google Scholar
8

Moore, K. J.; Tabas, I. Macrophages in the pathogenesis of atherosclerosis. Cell 2011, 145, 341–355.
DOI Google Scholar
9

Terashima, M.; Uchida, M.; Kosuge, H.; Tsao, P. S.; Young, M. J.; Conolly, S. M.; Douglas, T.; McConnell, M. V. Human ferritin cages for imaging vascular macrophages. Biomaterials 2011, 32, 1430–1437.
DOI Google Scholar
10

Rogers, I. S.; Tawakol, A. Imaging of coronary inflammation with fdg-pet: Feasibility and clinical hurdles. Curr. Cardiol. Rep. 2011, 13, 138–144.
DOI Google Scholar
11

Stone, G. W.; Maehara, A.; Lansky, A. J.; de Bruyne, B.; Cristea, E.; Mintz, G. S.; Mehran, R.; McPherson, J.; Farhat, N.; Marso, S. P. et al. A prospective natural-history study of coronary atherosclerosis. N. Engl. J. Med. 2011, 364, 226–235.
DOI Google Scholar
12

Tahara, N.; Mukherjee, J.; De Haas, H. J.; Petrov, A. D.; Tawakol, A.; Haider, N.; Tahara, A.; Constantinescu, C. C.; Zhou, J.; Boersma, H. H. et al. 2-Deoxy-2-[18F] fluoro-D-mannose positron emission tomography imaging in atherosclerosis. Nat. Med. 2014, 20, 215–219.
DOI Google Scholar
13

Weissleder, R.; Nahrendorf, M.; Pittet, M. J. Imaging macrophages with nanoparticles. Nat. Mater. 2014, 13, 125–138.
DOI Google Scholar
14

Lobatto, M. E.; Claudia, C.; Millon, A.; Senders, M. L.; Fay, F.; Robson, P. M.; Ramachandran, S.; Binderup, T.; Paridaans, M. P. M.; Sensarn, S. et al. Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles established by multimodal imaging. ACS Nano 2015, 9, 1837–1847.
DOI Google Scholar
15

Li, X.; Wang, C.; Tan, H.; Cheng, L. L.; Liu, G. B.; Yang, Y.; Zhao, Y. Z.; Zhang, Y. Q.; Li, Y. L.; Zhang, C. F. et al. Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques. Biomaterials 2016, 108, 71–80.
DOI Google Scholar
16

Tonga, G. Y.; Jeong, Y.; Duncan, B.; Mizuhara, T.; Mout, R.; Das, R.; Kim, S. T.; Yeh, Y. C.; Yan, B.; Hou, S. et al. Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts. Nat. Chem. 2015, 7, 597–603.
DOI Google Scholar
17

Wang, X. Y.; Hu, Y. H.; Wei, H. Nanozymes in bionanotechnology: From sensing to therapeutics and beyond. Inorg. Chem. Front. 2016, 3, 41–60.
DOI Google Scholar
18

Liu, B. W.; Liu, J. W. Surface modification of nanozymes. Nano Res. 2017, 10, 1125–1148.
DOI Google Scholar
19

Wei, H.; Wang, E. K. Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artificial enzymes. Chem. Soc. Rev. 2013, 42, 6060–6093.
DOI Google Scholar
20

Gao, N.; Dong, K.; Zhao, A. D.; Sun, H. J.; Wang, Y.; Ren, J. S.; Qu, X. G. Polyoxometalate-based nanozyme: Design of a multifunctional enzyme for multi-faceted treatment of Alzheimer's disease. Nano Res. 2016, 9, 1079–1090.
DOI Google Scholar
21

Wang, Z. Z.; Zhang, Y.; Ju, E. G.; Liu, Z.; Cao, F. F.; Chen, Z. W.; Ren, J. S.; Qu, X. G. Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors. Nat. Commun. 2018, 9, 3334.
DOI Google Scholar
22

Wei, H.; Wang, E. K. Fe3O4 magnetic nanoparticles as peroxidase mimetics and their applications in H2O2 and glucose detection. Anal. Chem. 2008, 80, 2250–2254.
DOI Google Scholar
23

Feng, L. Z.; Dong, Z. L.; Liang, C.; Chen, M. C.; Tao, D. L.; Cheng, L.; Yang, K.; Liu, Z. Iridium nanocrystals encapsulated liposomes as near-infrared light controllable nanozymes for enhanced cancer radiotherapy. Biomaterials 2018, 181, 81–91.
DOI Google Scholar
24

Gao, L. Z.; Zhuang, J.; Nie, L.; Zhang, J. B.; Zhang, Y.; Gu, N.; Wang, T. H.; Feng, J.; Yang, D. L.; Perrett, S. et al. Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat. Nanotechnol. 2007, 2, 577–583.
DOI Google Scholar
25

Liang, M. M.; Fan, K. L.; Pan, Y.; Jiang, H.; Wang, F.; Yang, D. L.; Lu, D.; Feng, J.; Zhao, J. J.; Yang, L. et al. Fe3O4 magnetic nanoparticle peroxidase mimetic-based colorimetric assay for the rapid detection of organophosphorus pesticide and nerve agent. Anal. Chem. 2012, 85, 308–312.
DOI Google Scholar
26

Zhuang, J.; Fan, K. L.; Gao, L. Z.; Lu, D.; Feng, J.; Yang, D. L.; Gu, N.; Zhang, Y.; Liang, M. M.; Yan, X. Y. Ex vivo detection of iron oxide magnetic nanoparticles in mice using their intrinsic peroxidase-mimicking activity. Mol. Pharm. 2012, 9, 1983–1989.
DOI Google Scholar
27

Fan, K. L.; Cao, C. Q.; Pan, Y. X.; Lu, D.; Yang, D. L.; Feng, J.; Song, L. N.; Liang, M. M.; Yan, X. Y. Magnetoferritin nanoparticles for targeting and visualizing tumour tissues. Nat. Nanotechnol. 2012, 7, 459–464.
DOI Google Scholar
28

Zhao, Y. Z.; Liang, M. M.; Li, X.; Fan, K. L.; Xiao, J.; Li, Y. L.; Shi, H. C.; Wang, F.; Choi, H. S.; Cheng, D. F. et al. Bioengineered magnetoferritin nanoprobes for single-dose nuclear-magnetic resonance tumor imaging. ACS Nano 2016, 10, 4184–4191.
DOI Google Scholar
29

Fan, K. L.; Xi, J. Q.; Fan, L.; Wang, P. X.; Zhu, C. H.; Tang, Y.; Xu, X. D.; Liang, M. M.; Jiang, B.; Yan, X. Y. et al. In vivo guiding nitrogen-doped carbon nanozyme for tumor catalytic therapy. Nat. Commun. 2018, 9, 1440.
DOI Google Scholar
30

Xu, Z. B.; Qiu, Z. Y.; Liu, Q.; Huang, Y. X.; Li, D. D.; Shen, X. G.; Fan, K. L.; Xi, J. Q.; Gu, Y. H.; Tang, Y. et al. Converting organosulfur compounds to inorganic polysulfides against resistant bacterial infections. Nat. Commun. 2018, 9, 3713.
DOI Google Scholar
31

Liang, M. M.; Fan, K. L.; Zhou, M.; Duan, D. M.; Zheng, J. Y.; Yang, D. L.; Feng, J.; Yan, X. Y. H-ferritin–nanocaged doxorubicin nanoparticles specifically target and kill tumors with a single-dose injection. Proc. Natl. Acad. Sci. USA 2014, 111, 14900–14905.
DOI Google Scholar
32

Ross, R. Atherosclerosis—An inflammatory disease. N. Engl. J. Med. 1999, 340, 115–126.
DOI Google Scholar
33

Ding, J. L.; Wang, Y. H.; Ma, M.; Zhang, Y.; Lu, S. S.; Jiang, Y. N.; Qi, C. M.; Luo, S. H.; Dong, G.; Wen, S. et al. CT/fluorescence dual-modal nanoemulsion platform for investigating atherosclerotic plaques. Biomaterials 2013, 34, 209–216.
DOI Google Scholar
34

Chinetti-Gbaguidi, G.; Colin, S.; Staels, B. Macrophage subsets in atherosclerosis. Nat. Rev. Cardiol. 2015, 12, 10–17.
DOI Google Scholar
35

Li, W.; Xu, L. H.; Forssell, C.; Sullivan, J. L.; Yuan, X. M. Overexpression of transferrin receptor and ferritin related to clinical symptoms and destabilization of human carotid plaques. Exp. Biol. Med. 2008, 233, 818–826.
DOI Google Scholar
36

Fargion, S.; Arosio, P.; Fracanzani, A. L.; Cislaghi, V.; Levi, S.; Cozzi, A.; Piperno, A.; Fiorelli, G. Characteristics and expression of binding sites specific for ferritin h-chain on human cell lines. Blood 1988, 71, 753–757.
DOI Google Scholar
37

Liang, M. M.; Tan, H.; Zhou, J.; Wang, T.; Duan, D. M.; Fan, K. L.; He, J. Y.; Cheng, D. F.; Shi, H. C.; Choi, H. S. et al. Bioengineered H-ferritin nanocages for quantitative imaging of vulnerable plaques in atherosclerosis. ACS Nano 2018, 12, 9300–9308.
DOI Google Scholar
38

Salacinski, P. R. P.; McLean, C.; Sykes, J. E. C.; Clement-Jones, V. V.; Lowry, P. J. Iodination of proteins, glycoproteins, and peptides using a solid-phase oxidizing agent, 1, 3, 4, 6-tetrachloro-3α, 6α-diphenyl glycoluril (iodogen). Anal. Biochem. 1981, 117, 136–146.
DOI Google Scholar
Publication history
Copyright
Acknowledgements

Publication history

Received: 07 December 2018
Revised: 23 January 2019
Accepted: 29 January 2019
Published: 05 March 2019
Issue date: April 2019

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Acknowledgements

Acknowledgements

This work was supported by the following grants: the National Key R & D Program of China (No. 2017YFA0205501), the National Natural Science Foundation of China (Nos. 81722024 and 81571728), the Key Research of Frontier Sciences (No. QYZDY-SSW-SMC013), and Youth Innovation Promotion Association of Chinese Academy of Sciences (No. 2014078).

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