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.

Macrophage Cell Membrane‐Cloaked Nanoplatforms for Biomedical Applications

“…In the experimental studies, the combination therapy with TN@AM NPs and NIR irradiation produced a significant decrease in both proinflammatory cytokine expression and viral count in the lungs, extended the survival time of the infected mice, and reduced lung tissue damage, indicating its potential to be used in clinical practice for the treatment of COVID-19 (Figure 17B-E). [47] In another recent effort to reduce the excessive inflammatory response associated with coronavirus infection, macrophagederived membranes were decorated onto PLGA NPs containing lopinavir, an antiviral drug, constructing a nanosystem with both antiviral and anti-inflammatory potential (Figure 18A). [160] The biomimetic nanoplatform expressed cytokine binding receptors, including IL-6R and IL-1βR, and could effectively absorb inflammatory cytokines and suppress macrophage and neutrophil activation, thereby alleviating the strong inflammatory response (Figure 18B,C).…”

“…In a recent effort to develop a multifunctional biomimetic nanosystem against COVID-19 infection, polymeric PLGA NP cores containing 2TPE-2NDTA, an efficient photothermal agent, were wrapped with alveolar macrophage-derived membranes (Figure 17A). [47] Under NIR irradiation, the biomimetic nanoplatform, called TN@AM NP, was highly efficient in converting NIR light into heat, even at very low concentrations, producing a substantial temperature increase for photothermal viral destruction, due to the high heat sensitivity of SARS-CoV-2. In the experimental studies, the combination therapy with TN@AM NPs and NIR irradiation produced a significant decrease in both proinflammatory cytokine expression and viral count in the lungs, extended the survival time of the infected mice, and reduced lung tissue damage, indicating its potential to be used in clinical practice for the treatment of COVID-19 (Figure 17B-E).…”

“…E) H&E staining images of pulmonary tissue recorder after 5 days of different treatments. Reproduced with permission [47]. Copyright 2021, Wiley-VCH GmbH.…”

Cell-derived membrane biomimetic nanocarriers for targeted therapy of pulmonary disease

“…In addition to the tumor targeting ability, macrophage biomimetic nanocarriers further showed the potential of anti-inflammatory and anti-virus. Nanoparticles coated by alveolar macrophage membrane demonstrated the ability as decoys to prevent coronavirus from entering host cells, absorbing a variety of pro-inflammatory cytokines, thereby reducing lung injury and inflammation ( Li et al, 2021b ).…”

The Variance of Photophysical Properties of Tetraphenylethene and Its Derivatives during Their Transitions from Dissolved States to Solid States

“…Since 2001, the terminology of aggregation-induced emission (AIE) was specifically cast by Tang et al [ 1 ] the value and potential of substantially enhanced emissions of organic compounds in aggregated solid states started to gain importance, especially for their advantages in overcoming the critical weaknesses of dyes including the aggregation-caused quenching (ACQ) of emission and the poor photobleaching characteristics [ 2 ]. Up to now, AIE luminogens (AIEgens) have been widely utilized in the fields of lighting [ 3 , 4 , 5 ], optical sensors [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ], biological therapies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ] and so on [ 21 , 22 , 23 , 24 , 25 , 26 ]. Hence, it shows the necessity to comprehensively understand the photophysical properties of AIEgens.…”