Repolarization of Inflammation-Associated Macrophages by Dual Drug-Loaded Liposomes for Acute Lung Sepsis Antibacterial and Anti-inflammatory Therapy

Abstract

Sepsis is defined as a systemic inflammatory response syndrome caused by a dysregulated host response to bacterial infection and is the leading cause of death in the intensive care unit at hospitals. At present, despite the discovery of many potential therapeutic methods for anti-infective treatment and immune-suppressing treatment, effective drug treatments for sepsis are lacking in the clinic. Herein, a coloaded dual therapeutic agent liposome (Cip·HCl/Cur@Lip-γ3) nanoplatform was developed by enveloping Cip·HCl and Cur into pH-responsive and inflammation-targeted liposomes. These liposomes simultaneously kill bacteria and regulate the polarization types of macrophages in infected lung tissue to relieve the infected microenvironment, providing antibacterial–anti-inflammatory therapy for synergetic acute lung sepsis. In vitro and in vivo results showed that Cip·HCl/Cur@Lip-γ3 exhibits excellent antibacterial properties against both Staphylococcus aureus and Pseudomonas aeruginosa and can effectively reduce inflammation and the immune response in acute lung infection. In addition, Cip·HCl/Cur@Lip-γ3 was administered to mice with acute lung infection, and the survival rate was 80% within 72 h. This study provides a nanoplatform to treat lung infection-induced sepsis, providing a strategy to design multifunctional nanomedicine for infectious disease therapy