Chen Min, Rosenberg Jillian, Cai Xiaolei, Lee Andy Chao Hsuan, Shi Jiuyun, Nguyen Mindy, Wignakumar Thirushan, Mirle Vikranth, Edobor Arianna Joy, Fung John, Donington Jessica Scott, Shanmugarajah Kumaran, Lin Yiliang, Chang Eugene, Randall Glenn, Penaloza-MacMaster Pablo, Tian Bozhi, Madariaga Maria Lucia, Huang Jun
Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, USA.
Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, USA.
Matter. 2021 Jun 2;4(6):2059-2082. doi: 10.1016/j.matt.2021.04.005. Epub 2021 Apr 22.
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 . Furthermore, the Nanotraps demonstrated an excellent biosafety profile and . Finally, the Nanotraps inhibited pseudotyped SARS-CoV-2 infection in live human lungs in an lung perfusion system. In summary, Nanotraps represent a new nanomedicine for the inhibition of SARS-CoV-2 infection.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)通过其病毒刺突蛋白与宿主细胞上的血管紧张素转换酶2(ACE2)受体结合进入宿主细胞。在此,我们表明,被称为“纳米陷阱”的功能化纳米颗粒通过阻断SARS-CoV-2刺突蛋白与宿主细胞ACE2之间的相互作用,完全抑制了SARS-CoV-2感染。基于脂质体的纳米陷阱表面用重组ACE2蛋白或抗SARS-CoV-2中和抗体以及吞噬作用特异性磷脂酰丝氨酸进行功能化修饰。纳米陷阱有效地捕获了SARS-CoV-2,并完全阻断了SARS-CoV-2对表达ACE2的人细胞系和原代肺细胞的感染;磷脂酰丝氨酸引发巨噬细胞对与病毒结合的、可生物降解的纳米陷阱的后续吞噬作用,导致假型病毒和真实病毒的清除。此外,纳米陷阱显示出优异的生物安全性。最后,纳米陷阱在肺灌注系统中抑制了活的人肺中的假型SARS-CoV-2感染。总之,纳米陷阱代表了一种用于抑制SARS-CoV-2感染的新型纳米药物。