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

ABSTRACT: 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. A therapeutic strategy for COVID‐19, based on multifunctional alveolar macrophage (AM)‐like nanoparticles (NPs), is successfully developed. The NPs display various AM receptors for coronavirus neutralization and proinflammatory cytokines absorption, thus achieving combined antiviral and anti‐inflammatory treatment. Furthermore, the photothermal feature of the NPs facilitates virus disruption under near‐infrared irradiation. This multimodal therapeutic regimen may be clinically applied for COVID‐19 management.

SUBMITTER: Li B

PROVIDER: S-EPMC8209923 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundUncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined.ResultsIn this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not.ConclusionThe i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.

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

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