A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2

Xiaolei Cai; Min Chen; Aleksander Prominski; Yiliang Lin; Nicholas Ankenbruck; Jillian Rosenberg; Mindy Nguyen; Jiuyun Shi; Anastasia Tomatsidou; Glenn Randall; Dominique Missiakas; John Fung; Eugene B. Chang; Pablo Penaloza-MacMaster; Bozhi Tian; Jun Huang

doi:10.1002/advs.202103240

A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2

Xiaolei Cai, Min Chen, Aleksander Prominski, Yiliang Lin, Nicholas Ankenbruck, Jillian Rosenberg, Mindy Nguyen, Jiuyun Shi, Anastasia Tomatsidou, Glenn Randall, Dominique Missiakas, John Fung, Eugene B. Chang, Pablo Penaloza-MacMaster, Bozhi Tian, Jun Huang^*

^*Corresponding author for this work

Microbiology-Immunology

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS-CoV-2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high-affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS-CoV-2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS-CoV-2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS-CoV-2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS-CoV-2 and its variants.

Original language	English (US)
Article number	2103240
Journal	Advanced Science
Volume	9
Issue number	2
DOIs	https://doi.org/10.1002/advs.202103240
State	Published - Jan 14 2022

Funding

The authors would like to thank Dr. Jeffrey Hubbell for the use of laboratory equipment. The authors would also like to thank Michal Raczy for his experimental guidance and Aaron Alpar for his support with blood analysis. This work was supported by NIH New Innovator award?DP2AI144245 (J.H.), NSF?Career award?1653782 (J. H.), and NIDDK RC2DK122394 (E. C.). N.A. is supported by NIH T32DK007074 and J.R. is supported by the NSF Graduate Research Fellowships Program DGE-1746045. All the in vitro and in vivo experiments were performed in accordance with the institutional guidelines following experimental protocols reviewed and approved by the Institutional Biosafety Committee and the Institutional Animal Care and Use Committee at the University of Chicago. The authors would like to thank Dr. Jeffrey Hubbell for the use of laboratory equipment. The authors would also like to thank Michal Raczy for his experimental guidance and Aaron Alpar for his support with blood analysis. This work was supported by NIH New Innovator award DP2AI144245 (J.H.), NSF Career award 1653782 (J. H.), and NIDDK RC2DK122394 (E. C.). N.A. is supported by NIH T32DK007074 and J.R. is supported by the NSF Graduate Research Fellowships Program DGE\u20101746045. All the in vitro and in vivo experiments were performed in accordance with the institutional guidelines following experimental protocols reviewed and approved by the Institutional Biosafety Committee and the Institutional Animal Care and Use Committee at the University of Chicago.

ASJC Scopus subject areas

Medicine (miscellaneous)
General Chemical Engineering
General Materials Science
Biochemistry, Genetics and Molecular Biology (miscellaneous)
General Engineering
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cai, X., Chen, M., Prominski, A., Lin, Y., Ankenbruck, N., Rosenberg, J., Nguyen, M., Shi, J., Tomatsidou, A., Randall, G., Missiakas, D., Fung, J., Chang, E. B., Penaloza-MacMaster, P., Tian, B., & Huang, J. (2022). A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2. Advanced Science, 9(2), Article 2103240. https://doi.org/10.1002/advs.202103240

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title = "A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2",

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, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS-CoV-2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high-affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS-CoV-2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS-CoV-2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS-CoV-2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS-CoV-2 and its variants.",

author = "Xiaolei Cai and Min Chen and Aleksander Prominski and Yiliang Lin and Nicholas Ankenbruck and Jillian Rosenberg and Mindy Nguyen and Jiuyun Shi and Anastasia Tomatsidou and Glenn Randall and Dominique Missiakas and John Fung and Chang, \{Eugene B.\} and Pablo Penaloza-MacMaster and Bozhi Tian and Jun Huang",

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Cai, X, Chen, M, Prominski, A, Lin, Y, Ankenbruck, N, Rosenberg, J, Nguyen, M, Shi, J, Tomatsidou, A, Randall, G, Missiakas, D, Fung, J, Chang, EB, Penaloza-MacMaster, P, Tian, B & Huang, J 2022, 'A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2', Advanced Science, vol. 9, no. 2, 2103240. https://doi.org/10.1002/advs.202103240

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T1 - A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2

AU - Cai, Xiaolei

AU - Chen, Min

AU - Prominski, Aleksander

AU - Lin, Yiliang

AU - Ankenbruck, Nicholas

AU - Rosenberg, Jillian

AU - Nguyen, Mindy

AU - Shi, Jiuyun

AU - Tomatsidou, Anastasia

AU - Randall, Glenn

AU - Missiakas, Dominique

AU - Fung, John

AU - Chang, Eugene B.

AU - Penaloza-MacMaster, Pablo

AU - Tian, Bozhi

AU - Huang, Jun

PY - 2022/1/14

Y1 - 2022/1/14

N2 - 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, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS-CoV-2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high-affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS-CoV-2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS-CoV-2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS-CoV-2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS-CoV-2 and its variants.

AB - 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, the current treatment options show limited curative efficacies. Here the authors report a strategy incorporating neutralizing antibodies conjugated to the surface of a photothermal nanoparticle (NP) to capture and inactivate SARS-CoV-2. The NP is comprised of a semiconducting polymer core and a biocompatible polyethylene glycol surface decorated with high-affinity neutralizing antibodies. The multifunctional NP efficiently captures SARS-CoV-2 pseudovirions and completely blocks viral infection to host cells in vitro through the surface neutralizing antibodies. In addition to virus capture and blocking function, the NP also possesses photothermal function to generate heat following irradiation for inactivation of virus. Importantly, the NPs described herein significantly outperform neutralizing antibodies at treating authentic SARS-CoV-2 infection in vivo. This multifunctional NP provides a flexible platform that can be readily adapted to other SARS-CoV-2 antibodies and extended to novel therapeutic proteins, thus it is expected to provide a broad range of protection against original SARS-CoV-2 and its variants.

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A Multifunctional Neutralizing Antibody-Conjugated Nanoparticle Inhibits and Inactivates SARS-CoV-2

Abstract

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UN SDGs

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