Acute Respiratory Distress Syndrome (ARDS) is a clinically
severe
respiratory disease that causes severe medical and economic burden.
To improve therapeutic efficacy, effectively targeting delivery to
the inflamed lungs and inflamed cells remains an ongoing challenge.
Herein, we designed engineered biomimetic nanovesicles (DHA@ANeu-DDAB)
by fusion of lung-targeting functional lipid, neutrophil membrane
containing activated β2 integrins, and the therapeutic
lipid, docosahexaenoic acid (DHA). By the advantage of lung targeting
lipid and β2 integrin targeting adhesion, DHA@ANeu-DDAB
can first target lung tissue and further target inflammatory vascular
endothelial cells, to achieve “tissue first, cell second”
hierarchical delivery. In addition, the β2 integrins
in DHA@ANeu-DDAB could bind to the intercellular cell adhesion molecule-1/2
(ICAM-1/2) ligand on the endothelium in the inflamed blood vessels,
thus inhibiting neutrophils’ infiltration in the blood circulation.
DHA administration to inflamed lungs could effectively regulate macrophage
phenotype and promote its anti-inflammatory activity via enhanced
biosynthesis of specialized pro-resolving mediators. In the lipopolysaccharide-induced
ARDS mouse model, DHA@ANeu-DDAB afforded a comprehensive and efficient
inhibition of lung inflammation and promoted acute lung damage repair.
Through mimicking physiological processes, these engineered biomimetic
vesicles as a delivery system possess good potential in targeting
therapy for ARDS.