Neutrophil membrane-mimicking nanodecoys with intrinsic anti-inflammatory properties alleviate sepsis-induced acute liver injury and lethality in a mouse endotoxemia model

Abstract

Sepsis-induced acute liver injury often develops in the early stages of sepsis and can exacerbate the pathology by contributing to multiple organ dysfunction and increasing lethality. No specific therapies for sepsis-induced liver injury are currently available; therefore, effective countermeasures are urgently needed. Considering the crucial role of neutrophils in sepsis-induced liver injury, herein, neutrophil membrane-mimicking nanodecoys (NM) were explored as a biomimetic nanomedicine for the treatment of sepsis-associated liver injury. NM administration exhibited excellent biocompatibility and dramatically decreased the plasma levels of inflammatory cytokines and liver injury biomarkers, including aspartate aminotransferase, alanine aminotransferase, and direct bilirubin, in a sepsis mouse model. NM treatment also reduced hepatic malondialdehyde content, myeloperoxidase activity, and histological injury, and ultimately improved survival in the septic mice. Further in vitro studies showed that NM treatment neutralized the neutrophil chemokines and inflammatory mediators and directly mitigated neutrophil chemotaxis and adhesion. Additionally, NM also markedly weakened lipopolysaccharide-induced reactive oxygen species generation, cyclooxygenase-2 expression, nitric oxide secretion, and subsequent hepatocyte injury. Thus, this study provides a promising therapeutic strategy for the management of sepsis-induced acute liver injury.

Keywords

• Sepsis
• Neutrophil infiltration
• Acute liver injury
• Nanovesicles
• Inflammatory mediators