Abstract
Cellular nanoparticles (CNPs), which refer to nanoparticles coated with natural cell membranes, are promising for neutralizing pathological agents. Here, we use CNPs as a medical countermeasure against the infection of SARS-CoV-2 variants in an animal model. CNPs comprise polymeric cores coated with the plasma membranes of human macrophages. The resulting nanoparticles (MΦ-NPs) act as host cell decoys to intercept SARS-CoV-2 and block its cellular entry, thus inhibiting subsequent viral infection. Our findings indicate that MΦ-NPs bind to the spike proteins of SARS-CoV-2 variants in a dose-dependent manner and inhibit the infectivity of live viruses. In hamsters infected with SARS-CoV-2 variants, MΦ-NPs significantly reduce the viral burden in the lungs, demonstrating their effectiveness in inhibiting viral infectivity in vivo. Furthermore, MΦ-NPs are primarily taken up by alveolar macrophages without inducing noticeable adverse effects. Given the crucial role of macrophages in viral infections, MΦ-NPs present a promising approach to combating emerging viral threats.