摘要：SummaryNovel treatment strategies are in urgent need to deal with the rapid development of antibiotic-resistant superbugs. Combination therapies and targeted drug delivery have been exploited to promote treatment efficacies. In this study, we loaded neutrophils with azithromycin and colistin to combine the advantages of antibiotic combinations, targeted delivery, and immunomodulatory effect of azithromycin to treat infections caused by Gram-negative pathogens. Delivery of colistin into neutrophils was mediated by fusogenic liposome, while azithromycin was directly taken up by neutrophils. Neutrophils loaded with the drugs maintained the abilitity to generate reactive oxygen species and migrate.In vitroassays demonstrated enhanced bactericidal activity against multidrug-resistant pathogens and reduced inflammatory cytokine production by the drug-loaded neutrophils. A single intravenous administration of the drug-loaded neutrophils effectively protected mice fromPseudomonas aeruginosainfection in an acute pneumonia model. This study provides a potential effective therapeutic approach for the treatment of bacterial infections.Graphical abstractDisplay OmittedHighlights•Neutrophils are loaded with colistin and azithromycinin vitro•The loaded drugs enhance the bactericidal effect and reduce the inflammatory response•Drug-loaded neutrophils conferred effective protection against bacterial infectionImmunology; Microbiology; Bacteriology
