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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\u2010based nanoantibiotics, which demonstrate an antibiotic adjuvant effect by inducing pH\u2010induced collapse and negative\u2010charged\u2010surface\u2010induced deformation. This enhances the disruption of the bacterial outer membrane and facilitates drug penetration, effectively boosting the antimicrobial activity against drug\u2010resistant 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\u2010resistant (MDR) <jats:italic>Escherichia coli<\/jats:italic> (clinical isolated strains) by up to 32\u2010fold. The survival rate of MDR <jats:italic>E. coli<\/jats:italic> 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.<\/jats:p>","DOI":"10.1002\/adhm.202401470","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T17:38:26Z","timestamp":1719423506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Action Programmed Nanoantibiotics with pH\u2010Induced Collapse and Negative\u2010Charged\u2010Surface\u2010Induced Deformation against Antibiotic\u2010Resistant Bacterial Peritonitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiao","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy Shandong Second Medical University  Weifang Shandong 261053 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penghui","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Bioscience and Technology Shandong Second Medical University  Weifang Shandong 261053 P. R. 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