Amphiphilic Nano-Swords for Direct Penetration and Eradication of Pathogenic Bacterial Biofilms
Cailing Zhou, Yu Zhou, Yaqian Zheng, Yue Yu, Kailing Yang, Zhiyong Chen, Xianhui Chen, Kang Wen, Yajie Chen, Silei Bai, Junfeng Song, Tong Wu, E Lei, Muyang Wan, Qingyun Cai, Z. Luyan, Wing‐Leung Wong, Yugang Bai, Chunhui Zhang, Xinxin Feng
Abstract
Bacterial biofilms are major causes of persistent and recurrent infections and implant failures. Biofilms are formable by most clinically important pathogens worldwide, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, causing recalcitrance to standard antibiotic therapy or anti-biofilm strategies due to amphiphilic impermeable extracellular polymeric substances (EPS) and the presence of resistant and persistent bacteria within the biofilm matrix. Herein, we report our design of an oligoamidine-based amphiphilic “nano-sword” with high structural compacity and rigidity. Its rigid, amphiphilic structure ensures effective penetration into EPS, and the membrane-DNA dual-targeting mechanism exerts strong bactericidal effect on the dormant bacterial persisters within biofilms. The potency of this oligoamidine is shown in two distinct modes of application: it may be used as a coating agent for polycaprolactone to fully inhibit surface biofilm growth in an implant-site mimicking micro-environment; meanwhile, it cures model mice of biofilm infections in various ex vivo and in vivo studies.