Inflammation-targeting nanoparticles impede neutrophil infiltration and scavenge ROS for acute lung injury alleviation.

Acute lung injury (ALI) is a severe acute diffuse lung disease caused by noncardiac factors, primarily associated with uncontrolled inflammation and excessive reactive oxygen species (ROS). In severe cases, ALI develops into acute respiratory distress syndrome (ARDS) with high mortality. The current clinical treatments of ALI have shown limited efficacy and fail to reduce mortality. The development of targeted therapeutic strategies presents significant clinical value and demand. Inspired by the fact that the neutrophils adhere to inflammatory endothelium and enter the inflammation site through PSGL-1/P-selectin interaction, we developed a P-selectin-binding platform termed LA NPs. Curcumin-loaded LA NPs (LA/Cur NPs) with multiple therapeutic modules bound to elevated P-selectin to target the inflammatory endothelium in the lung with ALI. Moreover, LA/Cur NPs reduced the infiltration of neutrophils by interfering with the PSGL-1/P-selectin interaction, suppressed the inflammation via the NF-κB pathway, and scavenged excessive reactive oxygen species (ROS), which eventually alleviated ALI in vivo. We provide a promising inflammation-targeting and ROS/inflammation suppression strategy for the treatment of ALI and other inflammatory lung diseases.