Macrophage membrane-coated polydopamine nanomedicine for treating acute lung injury through modulation of neutrophil extracellular traps and M2 macrophage polarization

Acute lung injury (ALI) is a life-threatening pulmonary inflammatory disorder with high morbidity and mortality rates. Effective targeting of damaged lung tissues and regulation of inflammatory dysregulation are major challenges in clinical treatment. This study aimed to develop a multifunctional drug delivery system by coating mesoporous polydopamine nanoparticles (mPDA NPs) loaded with Peimine (PM) using macrophage membranes (MMs) to leverage their inflammatory targeting properties. Both in vitro and in vivo experiments demonstrated the excellent targeting capability, strong antioxidant activity, and significant anti-inflammatory effects of the developed MM@mPDA-PM NPs. Furthermore, transcriptomics analysis revealed that MM@mPDA-PM NPs significantly reduced myeloperoxidase (MPO), neutrophil elastase (NE), and peptidylarginine deiminase 4 (PAD4), as well as inhibited the formation of neutrophil extracellular traps (NETs), and promoted M2 macrophage polarization by downregulating the NF-κB and JAK/STAT pathways. Our developed system effectively reduced neutrophil infiltration, suppressed cytokine storms, and regulated the pulmonary immune microenvironment, demonstrating great potential for treating ALI and other inflammatory diseases.