Phosphatidylserine-decorated delivery platform helps alleviate acute lung injury via potentiating macrophage targeting

Acute lung injury (ALI) is a life-threatening inflammatory disease with high morbidity and mortality. It is urgent to develop more effective therapeutic strategies against ALI. Phosphatidylserine (PtdSer) expressed on the surface of apoptotic cells not only allows for macrophage binding and recognition but also drives anti-inflammatory signaling within the macrophage. In this study, we designed an apoptotic cell-mimicry nanoparticle by decorating synthetic PtdSer on the outer face of nanoparticles. The results indicated that PtdSer-decorated poly(lactic-co-glycolic acid) nanoparticles (PSNPs) showed anti-inflammatory properties and increased macrophage phagocytosis in relative to the nondecorated poly(lactic-co-glycolic acid nanoparticles. Dexamethasone-loaded PSNPs exhibited superior anti-inflammatory activity on macrophages in vitro. In vivo studies also showed that PtdSer decoration increased the accumulation of nanoparticles in lung macrophages after pulmonary administration. Accumulation of dexamethasone-loaded PSNPs in lung macrophages effectively reduced inflammation in inflamed lungs and further alleviated ALI syndromes. In conclusion, PtdSer decoration not only endows the anti-inflammatory function to nanocarriers but also potentiates its macrophage targeting in the inflamed microenvironment, which offers an ideal drug delivery platform for ALI therapy.