Research Article

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2021, 14(5): 1260–1272

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https://doi.org/10.1007/s12274-020-3243-5

Manganese nanodepot augments host immune response against coronavirus

Yizhe Sun1, Yue Yin1, Lidong Gong1, Zichao Liang1, Chuanda Zhu1, Caixia Ren2, Nan Zheng3, Qiang Zhang4, Haibin Liu5, Wei Liu5, Fuping You1, Dan Lu1 (✉), and Zhiqiang Lin1 (✉)

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1 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
2 Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China
3 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), National Drug Clinical Trial Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
4 Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
5 Department of General Surgery, Xinjiang Production and Construction Corps Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830002, China

Keywords: interferon, coronavirus, manganese nanodepot (nanoMn), macrophage polarization, vaccine adjuvant
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  • Abstract
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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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Manganese nanodepot augments host immune response against coronavirus. Nano Res. 2021, 14(5): 1260–1272 https://doi.org/10.1007/s12274-020-3243-5

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