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

Sepsis is defined as a systemic inflammatory responsesyndromecaused by a dysregulated host response to bacterial infection andis the leading cause of death in the intensive care unit at hospitals.At present, despite the discovery of many potential therapeutic methodsfor anti-infective treatment and immune-suppressing treatment, effectivedrug treatments for sepsis are lacking in the clinic. Herein, a coloadeddual therapeutic agent liposome (Cip & BULL;HCl/Cur@Lip-& gamma;3) nanoplatformwas developed by enveloping Cip & BULL;HCl and Cur into pH-responsiveand inflammation-targeted liposomes. These liposomes simultaneouslykill bacteria and regulate the polarization types of macrophages ininfected lung tissue to relieve the infected microenvironment, providingantibacterial-anti-inflammatory therapy for synergetic acutelung sepsis. In vitro and in vivo results showed that Cip & BULL;HCl/Cur@Lip-& gamma;3exhibits excellent antibacterial properties against both Staphylococcus aureus and Pseudomonasaeruginosa and can effectively reduce inflammationand the immune response in acute lung infection. In addition, Cip & BULL;HCl/Cur@Lip-& gamma;3was administered to mice with acute lung infection, and the survivalrate was 80% within 72 h. This study provides a nanoplatform to treatlung infection-induced sepsis, providing a strategy to design multifunctionalnanomedicine for infectious disease therapy.