Biomimetic Lung-Targeting Nanoparticles with Antioxidative and Nrf2 Activating Properties for Treating Ischemia/Reperfusion-Induced Acute Lung Injury.

Ischemia/reperfusion (IR)-induced acute lung injury (ALI) has a high mortality rate. Reactive oxygen species (ROS) play a crucial role in causing cellular damage and death in IR-induced ALI. In this work, we developed a biomimetic lung-targeting nanoparticle (PC@MB) as an antioxidative lung protector for treating IR-induced ALI. PC@MBs showed excellent ROS scavenging and Nrf2 activation properties, along with a lung-targeting function through autologous cell membrane coating. The PC@MBs exhibited an impressive antioxidative and pulmonary protective role via redox homeostasis recovery through Nrf2 and heme oxygenase-1 activation. PC@MBs could maintain cell viability by effectively scavenging the intracellular ROS and restoring the redox equilibrium in the lesion. In the IR mouse model, the PC@MBs preferentially accumulated in the lung and distinctly repaired the pneumonic damage. Our strategy has the potential to offer a promising therapeutic paradigm for treating IR-induced ALI through the incorporation of different therapeutic mechanisms.