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HACE2-Exosome-Based Nano-Bait for Concurrent SARS-CoV-2 Trapping and Antioxidant Therapy

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    Biological and Medical Applications of Materials and Interfaces

    HACE2-Exosome-Based Nano-Bait for Concurrent SARS-CoV-2 Trapping and Antioxidant Therapy
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    • Xiaoyi Ma
      Xiaoyi Ma
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
      More by Xiaoyi Ma
    • Shiyu Guo
      Shiyu Guo
      Department of Pharmacology, Tongji University School of Medicine, Shanghai Tenth People’s Hospital, Shanghai 200092, P. R. China
      More by Shiyu Guo
    • Shuangrong Ruan
      Shuangrong Ruan
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
      More by Shuangrong Ruan
    • Yao Liu
      Yao Liu
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
      More by Yao Liu
    • Jie Zang
      Jie Zang
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
      More by Jie Zang
    • Yushan Yang
      Yushan Yang
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
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    • Haiqing Dong
      Haiqing Dong
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
      More by Haiqing Dong
      Orcidhttps://orcid.org/0000-0001-6428-5904
    • Yan Li
      Yan Li
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
      More by Yan Li
    • Tianbin Ren*
      Tianbin Ren
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
      *Email: [email protected]
      More by Tianbin Ren
    • Maomao An*
      Maomao An
      Department of Pharmacology, Tongji University School of Medicine, Shanghai Tenth People’s Hospital, Shanghai 200092, P. R. China
      *Email: [email protected]
      More by Maomao An
      Orcidhttps://orcid.org/0000-0003-2872-9074
    • Yongyong Li*
      Yongyong Li
      Shanghai Skin Disease Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, P. R. China
      *Email: [email protected]
      More by Yongyong Li
      Orcidhttps://orcid.org/0000-0002-6688-5978
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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2022, 14, 4, 4882–4891
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    https://doi.org/10.1021/acsami.1c19541
    Published January 22, 2022
    Copyright © 2022 American Chemical Society
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    Abstract

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    Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seriously threatening human health. Following SARS-CoV-2 infection, immune cell infiltration creates an inflammatory and oxidative microenvironment, which can cause pneumonia, severe acute respiratory syndrome, kidney failure, and even death. Clinically, a safe and effective treatment strategy remains to be established. Herein, a nano-bait strategy for inhibition of SARS-CoV-2 infection by redirecting viral attack while simultaneously relieving inflammation is developed. Specifically, the nano-bait was based on the exosome-sheathed polydopamine (PDA@Exosome) nanoparticles, which were generated by exocytosis of the PDA nanoparticles from H293T cells. In this approach, PDA@Exosome inherits from the source cells of H293T cells a surface display of ACE2 through pre-engineered expression. The resulting PDA@Exosome can compete with ACE2-expressing epithelial cells for S protein binding, in either the pre-exposure or post-exposure route. Moreover, relying on the ability of PDA to intercept and deactivate radical species, the PDA@Exosome can significantly attenuate the level of inflammatory cytokines by mediating oxidative stress, a major cause of organ injury. Due to its high trapping, multiple antioxidant ability, and good biocompatibility, the HACE2-exosome based nano-bait is a promising robust antiviral nanotherapeutics for the ongoing COVID-19 pandemic.

    Copyright © 2022 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsami.1c19541.

    • Hydrodynamic diameter of PDA@Exosome incubated in PBS with or without 10% FBS for different durations; phagocytosis of PDA by H293T cells characterized by a living cell workstation; investigation of the cellular uptake mechanism of PDA by using endocytosis inhibitors; time-dependent experiments of S protein binding to 293T cells characterized by living cell workstation; schematic illustration of the binding experiments; fluorescence images and semiquantitative analysis of cells after incubation with G5 and G6 groups; and fluorescence images of FITC-labeled S protein combined with PDA-Rho@Exosome (PDF)

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    ACS Applied Materials & Interfaces

    Cite this: ACS Appl. Mater. Interfaces 2022, 14, 4, 4882–4891
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsami.1c19541
    Published January 22, 2022
    Copyright © 2022 American Chemical Society
    Request reuse permissions

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