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Nano Research 2021, 14(5): 1260-1272 https://doi.org/10.1007/s12274-020-3243-5
Research Article | Issue | Published: 29 December 2020

Manganese nanodepot augments host immune response against coronavirus

Show Author's Information Yizhe Sun1,  Yue Yin1,  Lidong Gong1,  Zichao Liang1,  Chuanda Zhu1,  Caixia Ren2,  Nan Zheng3,  Qiang Zhang4,  Haibin Liu5,  Wei Liu5,  Fuping You1,  Dan Lu1( ),  Zhiqiang Lin1( )
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China
Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), National Drug Clinical Trial Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Department of General Surgery, Xinjiang Production and Construction Corps Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830002, China
Keywords:
coronavirus, interferon, manganese nanodepot (nanoMn), macrophage polarization, vaccine adjuvant
Topics:
MacrophagesManganeseMetal nanoparticlesViruses
Cite this article:
Sun Y, Yin Y, Gong L, et al. Manganese nanodepot augments host immune response against coronavirus. Nano Research, 2021, 14(5): 1260-1272. https://doi.org/10.1007/s12274-020-3243-5
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Abstract Full text Electronic supplementary material About this article

Interferon (IFN) responses are central to host defense against coronavirus and other virus infections. Manganese (Mn) is capable of inducing IFN production, but its applications are limited by nonspecific distributions and neurotoxicity. Here, we exploit chemical engineering strategy to fabricate a nanodepot of manganese (nanoMn) based on Mn2+. Compared with free Mn2+, nanoMn enhances cellular uptake and persistent release of Mn2+ in a pH-sensitive manner, thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo. Preferentially phagocytosed by macrophages, nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci, eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage. Besides, nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation, suggesting its potential as a vaccine adjuvant. Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese. Therefore, nanoMn offers a simple, safe, and robust nanoparticle-based strategy against coronavirus.


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Abstract
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Electronic supplementary material
About this article

Manganese nanodepot augments host immune response against coronavirus

Show Author's information Yizhe Sun1, Yue Yin1, Lidong Gong1, Zichao Liang1, Chuanda Zhu1, Caixia Ren2, Nan Zheng3, Qiang Zhang4, Haibin Liu5, Wei Liu5, Fuping You1, Dan Lu1( ), Zhiqiang Lin1( )
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center for Life Sciences, Peking University Health Science Center, Beijing 100191, China
Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), National Drug Clinical Trial Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Department of General Surgery, Xinjiang Production and Construction Corps Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830002, China

Abstract

Interferon (IFN) responses are central to host defense against coronavirus and other virus infections. Manganese (Mn) is capable of inducing IFN production, but its applications are limited by nonspecific distributions and neurotoxicity. Here, we exploit chemical engineering strategy to fabricate a nanodepot of manganese (nanoMn) based on Mn2+. Compared with free Mn2+, nanoMn enhances cellular uptake and persistent release of Mn2+ in a pH-sensitive manner, thus strengthening IFN response and eliciting broad-spectrum antiviral effects in vitro and in vivo. Preferentially phagocytosed by macrophages, nanoMn promotes M1 macrophage polarization and recruits monocytes into inflammatory foci, eventually augmenting antiviral immunity and ameliorating coronavirus-induced tissue damage. Besides, nanoMn can also potentiate the development of virus-specific memory T cells and host adaptive immunity through facilitating antigen presentation, suggesting its potential as a vaccine adjuvant. Pharmacokinetic and safety evaluations uncover that nanoMn treatment hardly induces neuroinflammation through limiting neuronal accumulation of manganese. Therefore, nanoMn offers a simple, safe, and robust nanoparticle-based strategy against coronavirus.

Keywords: coronavirus, interferon, manganese nanodepot (nanoMn), macrophage polarization, vaccine adjuvant

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Publication history
Copyright
Acknowledgements

Publication history

Received: 16 September 2020
Revised: 03 November 2020
Accepted: 14 November 2020
Published: 29 December 2020
Issue date: May 2021

Copyright

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

Acknowledgements

This work was supported by grants including the National Natural Science Foundation of China (Nos. 82022032 and 81991505 to D. L.), Clinical Medicine Plus X-Young Scholars Project, Peking University, the fundamental Research funds for the Central Universities (No. PKU2020LCXQ014 to D. L.), the Fundamental Research Funds for the Central Universities (No. BMU2018YJ003 to D. L., No. BMU2017YJ001 to Z. L.), and the Foundation from Science and Technology Bureau of Xinjiang production and Construction Corps (No. 2019BC006 to W. L.).

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