Abstract：
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.
摘要：
引入精心设计的抗生素纳米载体，以及抗生素佐剂作用，结合各种抗生素，为我们提供了对抗耐药菌株的机会。然而,当与抗生素一起使用时,对形态和包封的有效载荷释放的精确控制可以显著影响它们的抗菌功效和协同作用。这里,我们专注于开发基于脂肽的纳米抗生素，通过诱导pH诱导的塌陷和负电荷表面诱导的变形来证明抗生素佐剂作用。这增强了细菌外膜的破坏，促进了药物的渗透，有效增强抗耐药菌株的抗菌活性。具有模块化设计的脂肽纳米载体的调制规则由我们管理。纳米抗生素，由脂肽和环丙沙星（Cip）制成，具有超过80%的药物装载效率。与Cip的组合导致0.375的显著低的分数抑制浓度指数(FIC)和Cip对MDR大肠杆菌(临床分离菌株)的最小抑制浓度(MIC)显著降低高达32倍。我们的纳米抗生素治疗的MDR大肠杆菌腹膜炎的存活率明显更高，达到87%以上，相比之下，Cip只有25%，对照组没有生存率。同时,纳米抗生素对主要器官无明显毒性。本文受版权保护。保留所有权利。
