Abstract

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.

Highlights

  • Resolution is an active process that protects the host damage from inflammation responses induced by infections

  • Lung infections by P. aeruginosa is very common in hospitals and is life threatening to patients with complicated conditions at a very high mortality[4]

  • RvD1 binds to G protein-coupled receptors (GPCRs), decreasing the expression of adhesion molecules on endothelium, promoting the neutrophil apoptosis and enhancing the phagocytosis

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Summary

Introduction

Resolution is an active process that protects the host damage from inflammation responses induced by infections. We proposed a strategy to incorporate RvD1 and an antibiotic (ceftazidime) in human neutrophil-membrane derived nanovesicles that can target inflamed vasculature for treatment of lung infection caused by P. aeruginosa. Excessive/uncontrolled inflammation response may cause tissue injury, leading to a wide range of inflammatory disorders including ALI and sepsis[17,18,19,20,21]. Targeting both pathogens and host inflammatory pathways existing in infectious microenvironments may be a novel approach to mitigate infectious diseases. Delivering exogenous RvD1 may increase the inflammation resolution, but it is challenging to deliver RvD1 to inflammatory tissues in vivo

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