Action Programed Nanoantibiotics with pH-Induced Collapse and Negative-Charged-Surface-Induced Deformation Against Antibiotic-Resistant Bacterial Peritonitis.

The incorporation of well-designed antibiotic nanocarriers, along with an antibiotic adjuvant effect, in combination with various antibiotics, offers us an opportunity to combat drug-resistant strains. However, precise control over morphology and encapsulated payload release can significantly impact their antibacterial efficacy and synergistic effects when used alongside antibiotics. Here, we focus on developing lipopeptide-based nano-antibiotics, which demonstrate an antibiotic adjuvant effect by inducing pH-induced collapse and negative-charged-surface-induced deformation. This enhances the disruption of the bacterial outer membrane and facilitates drug penetration, effectively boosting the antimicrobial activity against drug-resistant strains. The modulation regulations of the lipopeptide nanocarriers with modular design were governed by us. The nanoantibiotics, made from lipopeptide and ciprofloxacin (Cip), have a drug loading efficiency of over 80%. The combination with Cip resulted in a significantly low fractional inhibitory concentration index (FIC) of 0.375 and a remarkable reduction in the minimum inhibitory concentration (MIC) of Cip against MDR E. coli (clinical isolated strains) by up to 32-fold. The survival rate of MDR E. coli peritonitis treated with our nanoantibiotics was significantly higher, reaching over 87%, compared to only 25% for Cip and no survival for the control group. Meanwhile, the nanoantibiotic showed no obvious toxicity to major organs. This article is protected by copyright. All rights reserved.