Dual-action membrane-chimeric liposomes with self-reinforcing targeting for acute lung injury treatment

Acute lung injury (ALI) is a common acute and critical syndrome with high mortality. The uncontrollable feedback loop of inflammation is the primary cause of death in patients with ALI. Therefore, targeting the inflammatory site and breaking the inflammatory loop are key strategies for ALI treatment. Our work developed a myeloid cell membrane-chimeric liposome containing dexamethasone (DEX) and leukocyte adhesin-1 (LA-1), abbreviated as ML/LA@DEX NPs. During the preparation of ML/LA@DEX NPs, LA-1 could activate CD11b on the myeloid cell membrane, thereby improving the binding ability of ML/LA@DEX NPs to ICAM-1 on endothelial cells in pulmonary inflammatory lesions, and achieving self-reinforcing targeting of ALI. ML/LA@DEX NPs accumulated at the inflammatory lesions would competitively occupy the binding site of neutrophils to reduce their recruitment. Meanwhile, ML/LA@DEX NPs would release DEX to inhibit the cytokine storm. Through this two-pronged approach, ML/LA@DEX NPs effectively broke the positive feedback loop of inflammation and showed significant therapeutic effects on ALI, providing a new strategy for ALI treatment.