DisruptingBiofilm Tolerance by Ionic Microbubble-MediatedCopper Ion Surge for Infection Clearance

作者：Xiaoye Li, Qiang Li, Ao He, Meng Dang, Yu Zhang, Minjin Wang, Qinhong Sun, Zhuo Dai, Meng Ding, Jinjin Zheng, Yongbin Mou, Weijun Xiu, Heng Dong · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.5c08035 · 被引用次数：40 · 研究领域：Bacterial biofilms and quorum sensing、Biosensors and Analytical Detection、Water Treatment and Disinfection

Abstract Bacterial infections caused by drug-resistant bacteria persist due to biofilm-mediated tolerance, which limits the efficacy of both antimicrobial agents and host immune defenses. Here, we develop ionic microbubbles (MB-CuTA) self-assembled by Fe3O4@CuTA nanoparticles to enhance copper ion-mediated antibiofilm therapy. Upon ultrasound activation, MB-CuTA undergoes inertial cavitation, disrupting biofilm integrity and generating a localized surge of copper ions. This process achieves a dual therapeutic effect: (1) disruption of bacterial metabolic homeostasis, thereby overcoming the intrinsic resistance of biofilms to conventional antimicrobial agents, and (2) activation of cellular immunity to effectively counteract bacterial immune evasion mechanisms. By breaking biofilm tolerance through both metabolic and immunological pathways, our strategy enables deep copper ion penetration in biofilms and effective infection clearance in both mouse implant infection and peritonitis infection models. Our approach introduces a biofilm tolerance disruption method through inducing bacterial cuproptosis-like death and cellular immunity activation, offering a promising strategy against biofilm infections.