Neutrophil Targeting Lipid Nanoparticle Alleviates SARS-CoV-2–Induced Pulmonary Injury and Inflammation
발표자
이석희 (성균관대학교)
연구책임자
박우람 (성균관대학교)
초록
내용
Excessive neutrophil activation, including neutrophil extracellular trap (NET) formation, is associated with severe COVID-19 and long-term sequelae, yet clinical applications of neutrophil-targeting therapies are limited by their short half-life and insufficient cell-type specificity. This study developed a lipid nanoparticle (LNP) platform designated DPN-LNPs, that co-encapsulates two NET inhibitors, DNase I and sivelestat, for specific delivery to lung neutrophils. In vitro and in vivo studies demonstrate that DPN-LNPs preferentially accumulate in lung neutrophils and degrade NETs as efficiently as free DNase I and sivelestat. Notably, DPN-LNP treatment administered only during the symptomatic phase of infection significantly improved SARS-CoV-2 outcomes. These findings provide proof-of-concept for adapting the LNP platform to deliver multiple immunomodulatory drugs in a cell-type specific manner to manage NET-associated complications in COVID-19 and other lung diseases.