Antiviral and Anti‐Inflammatory Treatment with Multifunctional Alveolar Macrophage‐Like Nanoparticles in a Surrogate Mouse Model of COVID‐19

Abstract The pandemic of coronavirus disease 2019 (COVID‐19) is continually worsening. Clinical treatment for COVID‐19 remains primarily supportive with no specific medicines or regimens. Here, the development of multifunctional alveolar macrophage (AM)‐like nanoparticles (NPs) with photothermal inactivation capability for COVID‐19 treatment is reported. The NPs, made by wrapping polymeric cores with AM membranes, display the same surface receptors as AMs, including the coronavirus receptor and multiple cytokine receptors. By acting as AM decoys, the NPs block coronavirus from host cell entry and absorb various proinflammatory cytokines, thus achieving combined antiviral and anti‐inflammatory treatment. To enhance the antiviral efficiency, an efficient photothermal material based on aggregation‐induced emission luminogens is doped into the NPs for virus photothermal disruption under near‐infrared (NIR) irradiation. In a surrogate mouse model of COVID‐19 caused by murine coronavirus, treatment with multifunctional AM‐like NPs with NIR irradiation decreases virus burden and cytokine levels, reduces lung damage and inflammation, and confers a significant survival advantage to the infected mice. Crucially, this therapeutic strategy may be clinically applied for the treatment of COVID‐19 at early stage through atomization inhalation of the NPs followed by NIR irradiation of the respiratory tract, thus alleviating infection progression and reducing transmission risk.