Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections.

Cytokine storms are a primary cause of multiple organ damage and death after severe infections, such as SARS-CoV-2. However, current single cytokine-targeted strategies display limited therapeutic efficacy. Here, we report that peritoneal M2 macrophage-derived extracellular vesicles (M2-EVs) are multitarget nanotherapeutics that can be used to resolve cytokine storms. In detail, primary peritoneal M2 macrophages exhibited superior anti-inflammatory potential than immobilized cell lines. Systemically administered M2-EVs entered major organs and were taken up by phagocytes (e.g., macrophages). M2-EV treatment effectively reduced excessive cytokine (e.g., TNF-α and IL-6) release in vitro and in vivo, thereby attenuating oxidative stress and multiple organ (lung, liver, spleen and kidney) damage in endotoxin-induced cytokine storms. Moreover, M2-EVs simultaneously inhibited multiple key proinflammatory pathways (e.g., NF-κB, JAK-STAT and p38 MAPK) by regulating complex miRNA-gene and gene-gene networks, and this effect was collectively mediated by many functional cargos (miRNAs and proteins) in EVs. In addition to the direct anti-inflammatory role, human peritoneal M2-EVs expressed angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV-2 spike protein, and thus could serve as nanodecoys to prevent SARS-CoV-2 pseudovirus infection in vitro. As cell-derived nanomaterials, the therapeutic index of M2-EVs can be further improved by genetic/chemical modification or loading with specific drugs. This study highlights that peritoneal M2-EVs are promising multifunctional nanotherapeutics to attenuate infectious disease-related cytokine storms.

Considerations in treating patients with advance lung cancer during the epidemic outbreak of novel coronavirus (SARS-CoV-2).

The outbreak of pneumonia caused by novel coronavirus (SARS-CoV-2) in Wuhan, China, at the end of 2019 quickly escalated into a global health emergency. Since its outbreak until the 29th of April 2020, the pandemic has affected more than 3 million of people and caused 207,973 deaths globally. SARS-CoV-2 belongs to the ß-coronavirus genus of the Coronavirus family, and it shares the same subfamily with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome-associated coronavirus (MERS-CoV), all of which lead to severe pneumonia. For cancer patients, especially those with lung cancers, their immune systems are compromised due to the disease itself as well as the treatment for cancer. The weakened immunity of these patients puts them at a higher risk of not only developing diseases but severe diseases. In this study, through a literature review and data collection, we focus on the selection and consideration of antitumor treatment strategies for advanced lung cancer during the coronavirus disease 2019 (COVID-19) epidemic.