TY - JOUR
T1 - Nanotraps for the containment and clearance of SARS-CoV-2
AU - Chen, Min
AU - Rosenberg, Jillian
AU - Cai, Xiaolei
AU - Hsuan Lee, Andy Chao
AU - Shi, Jiuyun
AU - Nguyen, Mindy
AU - Wignakumar, Thirushan
AU - Mirle, Vikranth
AU - Edobor, Arianna Joy
AU - Fung, John
AU - Donington, Jessica Scott
AU - Shanmugarajah, Kumaran
AU - Lin, Yiliang
AU - Chang, Eugene
AU - Randall, Glenn
AU - Penaloza-MacMaster, Pablo
AU - Tian, Bozhi
AU - Madariaga, Maria Lucia
AU - Huang, Jun
N1 - Funding Information:
This work was supported by NIH New Innovator award 1DP2AI144245 (J.H.), NSF Career award 1653782 (J.H.), and NIDDK RC2DK122394 (E.C.). M.C. is partially supported by the UChicago Big Ideas Generator Grant. J.R. is supported by the NSF Graduate Research Fellowships Program DGE-1746045 . We would like to thank Dr. Nicholas Ankenbruck, Yifei Hu, Guoshuai Cao, Ruyi Wang, Joe Reda, and Aaron Alpar for their experimental guidance. P.P.M. is supported by DP2DA051912 . We would also like to thank Dr. Aaron Esser-Kahn for kindly providing THP-1 cells, Dr. Jeffery Hubbell for the use of laboratory equipment, and Dr. Shann Yu for kindly ordering C57BL/6NHsd mice during the pandemic. We also acknowledge the support from the University of Chicago Human Tissue Research Center, University of Chicago Integrated Light Microscopy Core, and the Soft Matter Characterization Facility of the Pritzker School of Molecular Engineering for sample processing and characterization.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6/2
Y1 - 2021/6/2
N2 - SARS-CoV-2 enters host cells through its viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells. Here, we show that functionalized nanoparticles, termed “Nanotraps,” completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells. The liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and phagocytosis-specific phosphatidylserines. The Nanotraps effectively captured SARS-CoV-2 and completely blocked SARS-CoV-2 infection to ACE2-expressing human cell lines and primary lung cells; the phosphatidylserine triggered subsequent phagocytosis of the virus-bound, biodegradable Nanotraps by macrophages, leading to the clearance of pseudotyped and authentic virus in vitro. Furthermore, the Nanotraps demonstrated an excellent biosafety profile in vitro and in vivo. Finally, the Nanotraps inhibited pseudotyped SARS-CoV-2 infection in live human lungs in an ex vivo lung perfusion system. In summary, Nanotraps represent a new nanomedicine for the inhibition of SARS-CoV-2 infection.
AB - SARS-CoV-2 enters host cells through its viral spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells. Here, we show that functionalized nanoparticles, termed “Nanotraps,” completely inhibited SARS-CoV-2 infection by blocking the interaction between the spike protein of SARS-CoV-2 and the ACE2 of host cells. The liposomal-based Nanotrap surfaces were functionalized with either recombinant ACE2 proteins or anti-SARS-CoV-2 neutralizing antibodies and phagocytosis-specific phosphatidylserines. The Nanotraps effectively captured SARS-CoV-2 and completely blocked SARS-CoV-2 infection to ACE2-expressing human cell lines and primary lung cells; the phosphatidylserine triggered subsequent phagocytosis of the virus-bound, biodegradable Nanotraps by macrophages, leading to the clearance of pseudotyped and authentic virus in vitro. Furthermore, the Nanotraps demonstrated an excellent biosafety profile in vitro and in vivo. Finally, the Nanotraps inhibited pseudotyped SARS-CoV-2 infection in live human lungs in an ex vivo lung perfusion system. In summary, Nanotraps represent a new nanomedicine for the inhibition of SARS-CoV-2 infection.
KW - COVID-19
KW - MAP6: Development
KW - SARS-CoV-2
KW - antiviral
KW - inhibition
KW - macrophage
KW - nanomedicine
KW - nanoparticle
KW - treatment
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U2 - 10.1016/j.matt.2021.04.005
DO - 10.1016/j.matt.2021.04.005
M3 - Article
C2 - 33907732
AN - SCOPUS:85104977442
SN - 2590-2393
VL - 4
SP - 2059
EP - 2082
JO - Matter
JF - Matter
IS - 6
ER -