Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.

The current outbreak of the beta-coronavirus (beta-Cov) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in December 2019. No specific antiviral treatments or vaccines are currently available. A recent study has reported that coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2 infection, is associated with neutrophil-specific plasma membrane rupture, and release excessive neutrophil extracellular traps (NETs) and extracellular DNAs (eDNAs). This mechanism involves the activation of NETosis, a neutrophil-specific programmed cell death, which is believed to play a crucial role in COVID-19 pathogenesis. Further progression of the disease can cause uncontrolled inflammation, leading to the initiation of cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. Herein, it is reported that DNase-I-coated melanin-like nanospheres (DNase-I pMNSs) mitigate sepsis-associated NETosis dysregulation, thereby preventing further progression of the disease. Recombinant DNase-I and poly(ethylene glycol) (PEG) are used as coatings to promote the lengthy circulation and dissolution of NET structure. The data indicate that the application of bioinspired DNase-I pMNSs reduce neutrophil counts and NETosis-related factors in the plasma of SARS-CoV-2 sepsis patients, alleviates systemic inflammation, and attenuates mortality in a septic mouse model. Altogether, the findings suggest that these nanoparticles have potential applications in the treatment of SARS-CoV-2-related illnesses and other beta-CoV-related diseases.

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Layered double hydroxides (LDHs) with two-dimensional nanostructure are inorganic materials that have attractive advantages such as biocompatibility, facile preparation, and high drug loading capacity for therapeutic bioapplications. Since the intercalation chemistry of DNA molecules into the LDH materials were reported, various LDH nanohybrids have been developed for biomedical drug delivery system. For these reasons, LDHs hybridized with numerous therapeutic agents have a significant role in cancer imaging and therapy with targeting functions. In this review, we summarized the recent advances in the preparation of LDH nanohybrids for cancer therapeutic strategies including gene therapy, chemotherapy, immunotherapy, and combination therapy.

In the originally published article, there was an error in Figure 4. Please find the correct Figure 4 here: Figure 4. Cytokine levels in the lung tissue in CLP-operated mouse model. Heat map of inflammation-related genes in the lung tissue after DNase-I pMNSs treatment (n = 3). CLP, Cecal ligation and perforation; pMNSs: PEG-coated melanin-like nanospheres.