Treating acute lung injury through scavenging of cell-free DNA by cationic nanoparticles.

Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions induced by inflammatory responses, in which cell-free DNA (cfDNA) plays a pivotal role. This study investigated the therapeutic potential of biodegradable cationic nanoparticles (cNPs) in alleviating ALI. Using a mouse model of lipopolysaccharide-induced ALI, we examined the impact of intravenously administered cNPs. Our findings indicate that cNPs possess robust DNA binding capability, enhanced accumulation in inflamed lungs, and a favorable safety profile . Furthermore, cNPs attenuate the inflammatory response in LPS-induced ALI mice by scavenging cfDNA, mainly derived from neutrophil extracellular traps, and activating the macrophage-mediated cGAS-STING pathway. The findings suggest a potential treatment for ALI by targeting cfDNA with cNPs. This approach has demonstrated efficacy in mitigating lung injury and merits further exploration.