A Neutralizing Antibody-Conjugated Photothermal Nanoparticle Captures and Inactivates SARS-CoV-2

  1. Xiaolei Cai
  2. Aleksander Prominski
  3. Yiliang Lin
  4. Nicholas Ankenbruck
  5. Jillian Rosenberg
  6. Min Chen
  7. Jiuyun Shi
  8. Eugene B. Chang
  9. Pablo Penaloza-MacMaster
  10. Bozhi Tian
  11. Jun Huang

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Abstract

The outbreak of 2019 coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic. Despite intensive research including several clinical trials, currently there are no completely safe or effective therapeutics to cure the disease. Here we report a strategy incorporating neutralizing antibodies conjugated on the surface of a photothermal nanoparticle to actively capture and inactivate SARS-CoV-2. The photothermal nanoparticle is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with neutralizing antibodies. Such nanoparticles displayed efficient capture of SARS-CoV-2 pseudoviruses, excellent photothermal effect, and complete inhibition of viral entry into ACE2-expressing host cells via simultaneous blocking and inactivating of the virus. This photothermal nanoparticle is a flexible platform that can be readily adapted to other SARS-CoV-2 antibodies and extended to novel therapeutic proteins, thus providing a broad range of protection against multiple strains of SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.30.404624: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-SARS-CoV-2 neutralizing antibodies were added into the nanoparticle solution with a mass ratio of 1:10 (antibody: DSPE-PEG2000-NHS) and stirred overnight at 4 °C to complete the conjugation.
    Anti-SARS-CoV-2 neutralizing
    suggested: None
    Fluorescent Imaging of Photothermal Nanoparticles: The photothermal nanoparticles (100 μg/mL, 10 μL) was incubated with the secondary Alexa Fluor 488-labeled anti-IgG2b antibody (100 μg/mL, 10 μL) for 1 h.
    anti-IgG2b
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    In Vitro Viral Infection of SARS-CoV-2 VSV-GFP Pseudovirus: ACE2/HEK293T cells (5 × 104 cells) were seeded into 96-well plates (flat bottom, GenClone®) and incubated overnight at 37 °C in a humified CO2 incubator.
    ACE2/HEK293T
    suggested: None
    Software and Algorithms
    SentencesResources
    The numbers of total cells and infected cells were counted in ImageJ using the following workflow: Adjust→Threshold (Otsu), Process→Binary→Fill Holes→Watershed, Analyze→ Analyze Particles.
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.11.30.404624v1 on bioRxiv