Co-delivery of resolvin D1 and antibiotics with nanovesicles to lungs resolves inflammation and clears bacteria in mice

• Published in: Communications biology 2020-11, Vol.3 (1), p.680-680, Article 680
• Main Authors: Gao, Jin, Wang, Sihan, Dong, Xinyue, Leanse, Leon G., Dai, Tianhong, Wang, Zhenjia
• Format: Article
• Language: English
• Subjects: 14; 59; 59/5; 631/154/152; 631/61/350/354; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antibiotics; Bacteria; Bacterial infections; Biology; Biomedical and Life Sciences; Bronchopulmonary infection; Cavitation; Ceftazidime; Ceftazidime - administration & dosage; Ceftazidime - therapeutic use; Cytokines; Docosahexaenoic Acids - administration & dosage; Docosahexaenoic Acids - therapeutic use; Drug Delivery Systems; Human Umbilical Vein Endothelial Cells; Humans; Infections; Infectious diseases; Inflammation; Inflammation - drug therapy; Inflammation - microbiology; Leukocytes (neutrophilic); Life Sciences; Lungs; Male; Mice; Nanoparticles; Nanostructures; Neutrophils; Pathogens; Pneumonia, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections - drug therapy; Pseudomonas Infections - microbiology
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-01410-5

Resolution is an active process that protects the host damage from inflammation responses induced by infections. Simultaneously resolving inflammation and eliminating pathogens may be effective to treat infectious diseases, but it is required to deliver therapeutics to infectious sites. Here, we proposed a strategy to incorporate RvD1 and an antibiotic (ceftazidime) in human neutrophil-membrane derived nanovesicles that can specifically target inflamed vasculature for treatment of lung infection caused by P. aeruginosa . Using the nitrogen cavitation method, we generated liposome-like nanovesicles from human neutrophil membrane. The results showed that nanovesicles loaded with RvD1 decreased cytokine levels and neutrophil lung infiltration, thus shortening the resolution intervals of lung inflammation. When RvD1 and ceftazidime were co-loaded in nanovesicles, they alleviated both inflammation and bacterial growth in the mouse lung. The studies reveal a new strategy to treat infectious diseases by designing nanoparticles to simultanesouly target host inflammatory pathways and pathogens. Gao et al. design a lung targeting nanovesicles made from human neutrophils membrane, and co-loaded inflammatory resolving mediator RvD1 and antibiotic CAZ inside the nanovesicles. These nanovesicles could accelerate the inflammation resolution and release the antibiotics to treat bacterial infections in mice. This approach is useful in developing multifunctional nanoparticle-based therapeutics for lung bacterial infections treatment.