Engineered Biomimetic Nanovesicles Based on Neutrophils for Hierarchical Targeting Therapy of Acute Respiratory Distress Syndrome.
ACS Nano
; 18(2): 1658-1677, 2024 Jan 16.
Article
in En
| MEDLINE
| ID: mdl-38166370
ABSTRACT
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 ß2 integrins, and the therapeutic lipid, docosahexaenoic acid (DHA). By the advantage of lung targeting lipid and ß2 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 ß2 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory Distress Syndrome
/
Quaternary Ammonium Compounds
/
Neutrophils
Limits:
Animals
/
Humans
Language:
En
Journal:
ACS Nano
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United States