Fluorous‐Tagged Peptide Nanoparticles Ameliorate Acute Lung Injury via Lysosomal Stabilization and Inflammation Inhibition in Pulmonary Macrophages

Abstract Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common respiratory critical syndrome that currently has no effective therapeutic interventions. Pulmonary macrophages play a principal role in the initiation and progression of the overwhelming inflammation in ALI/ARDS. Here, a type of fluorous‐tagged bioactive peptide nanoparticle termed CFF13F is developed, which can be efficiently internalized by macrophages and suppress the excessive expression of cytokines and the overproduction of reactive oxygen species (ROS) triggered by lipopolysaccharide (LPS). The cytoprotective effect of CFF13F may be attributed to the lysosomal‐stabilization property and regulation of the antioxidative system. Moreover, intratracheal pretreatment with CFF13F can effectively reduce local and systematic inflammation, and ameliorate pulmonary damage in an LPS‐induced ALI murine model. The therapeutic efficacy of CFF13F is affected by the administration routes, and the local intratracheal injection is found to be the optimal choice for ALI treatment, with preferred biodistribution profiles. The present study provides solid evidence of the potent immunomodulatory bioactivity of the fluorous‐tagged peptide nanoparticles CFF13F in vitro and in vivo, and sheds light on the development of novel efficient nanodrugs for ALI/ARDS.