Repolarization of inflammation-associated macrophages by multifunctional dual drug-loaded liposome with antibacterial capacity for acute lung sepsis synergistic therapy

Abstract Background Sepsis is defined 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. Results Herein, a novel coloaded dual therapeutic agent liposomes (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 type of macrophages in infected lung tissue to relieve the infected microenvironment, providing antibacterial-anti-inflammatory therapy for synergetic acute lung sepsis antibacterial-anti-inflammatory therapy. In vitro and in vivo results showed that Cip·HCl/Cur@Lip-γ3 exhibits excellent antibacterial properties against both S. aureus and P. 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. Conclusion This study provides a novel nanoplatform to treat lung infection-induced sepsis, providing a new strategy to design multifunctional nanomedicine for infectious disease therapy.