Apoptotic neutrophil-mediated inflammatory microenvironment regulation for the treatment of ARDS

Abstract

Acute respiratory distress syndrome (ARDS) is a critical respiratory disease characterized by uncontrolled acute lung inflammation with high mortality. At present, effective therapeutic drugs for clinical practice are still lacking. Neutrophil apoptosis and subsequent efferocytosis by macrophages can modulate the lung inflammatory microenvironment of ARDS, thereby promoting the repair of injured lungs. Inspired by the spontaneous process and immunomodulatory properties of apoptotic neutrophils, an apoptotic neutrophil-mediated drug delivery system (T-NP@ApoNEs) for ARDS treatment was constructed. After intravenous injection, T-NP@ApoNEs could adhere to the inflammatory vascular endothelial cells and thus accumulate in the inflamed lung, which were then efficiently phagocytized by macrophages through efferocytosis. Apoptotic neutrophils and pre-loaded anti-inflammatory drug TPCA-1 could synergistically regulate the inflammatory microenvironment of ARDS lungs. It exhibited significant effects on reducing neutrophil infiltration, inhibiting cytokine storm, and promoting macrophage polarization into anti-inflammatory phenotype. In summary, the apoptotic neutrophil-mediated drug delivery strategy may provide an effective therapeutic modality for ARDS.