Action Programmed 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 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, this study focuses on developing lipopeptide‐based nanoantibiotics, 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 are governed by the authors. The nanoantibiotics, made from lipopeptide and ciprofloxacin (Cip), have a drug loading efficiency of over 80%. The combination with Cip results in a significantly low fractional inhibitory concentration index of 0.375 and a remarkable reduction in the minimum inhibitory concentration of Cip against multidrug‐resistant (MDR) Escherichia coli (clinical isolated strains) by up to 32‐fold. The survival rate of MDR E. coli peritonitis treated with nanoantibiotics is significantly higher, reaching over 87%, compared to only 25% for Cip and no survival for the control group. Meanwhile, the nanoantibiotic shows no obvious toxicity to major organs. The focus of this article is on the development of lipopeptide‐based nanoantibiotics that show antibiotic adjuvant effects by inducing pH‐induced collapse and deformation caused by negatively charged surfaces. This enhances the disruption of the bacterial outer membrane, facilitates drug penetration, and effectively improves antibacterial activity against drug‐resistant strains. The modulation rules of modularly designed lipopeptide nanocarriers are investigated.