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Nano Research

Article Title

Manganese nanodepot augments host immune response against coronavirus

Authors

Yizhe Sun, 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
Yue Yin, 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
Lidong Gong, 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
Zichao Liang, 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
Chuanda Zhu, 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
Caixia Ren, Department of Human Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China
Nan Zheng, Key Laboratory of Carcinogenesis and Translational Research , National Drug Clinical Trial Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
Qiang Zhang, Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Haibin Liu, Department of General Surgery, Xinjiang Production and Construction Corps Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830002, China
Wei Liu, Department of General Surgery, Xinjiang Production and Construction Corps Hospital, Urumchi, Xinjiang Uygur Autonomous Region 830002, China
Fuping You, 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
Dan Lu, 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
Zhiqiang Lin, 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

Keywords

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

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.

Publisher

Tsinghua University Press

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