TY - JOUR
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
N1 - Funding Information:
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.
Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
PY - 2021
Y1 - 2021
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.
KW - COVID-19
KW - SARS-CoV-2
KW - multifunctional nanoparticle
KW - photothermal therapy
KW - virus inactivation
UR - http://www.scopus.com/inward/record.url?scp=85118779715&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85118779715&partnerID=8YFLogxK
U2 - 10.1002/advs.202103240
DO - 10.1002/advs.202103240
M3 - Article
C2 - 34761549
AN - SCOPUS:85118779715
JO - Advanced Science
JF - Advanced Science
SN - 2198-3844
ER -