Peptide-based nano-antibiotic transformers with antibiotic adjuvant effect for multidrug resistant bacterial pneumonia therapy

Antibiotic-resistance is a growing threat since it endangers the antibiotic treatments such as surgery, transplants and skin damage, which may cause the top-risk of death to public in 2050. Here, we fabricated nano-antibiotic transformers ( NATs ) that co-assembled with two lipopeptides and loaded with antibiotics. Once specifically bonding onto the bacterial membrane through multi-targeting of Lipo-20 , our NATs activated the in-situ nanofiber deformation, which enhanced membrane disruption and antibiotic penetration resulting in antibiotic adjuvant effect (FICI=0.3, 8-fold reduced the MIC of antibiotic). Meanwhile, the transformed nanofiber further trapped the bacteria similar as the neutrophil extracellular traps (NETs) to enhance the clearance of bacteria in vivo . Additionally, the optimized ratios of two components of lipopeptides maintained the high antibiotic adjuvant activity and more significantly reduced hemolysis. Our NATs significantly prolong the life-time of antibiotic without resistance appear over one month. Finally, the clinical isolated antibiotic-resistance Klebsiella pneumoniae induced pneumonia can be cured based on the synergistic interactions of antibiotic adjuvant activity and targeted antibiotic delivery. We believed such nanotranformers will offer us a broadly applicable drug-delivery system for antibiotic-resistance infection in vivo .