Amphiphilic Janus Nanoparticles Synergize with Antibiotics to Restore Susceptibility in Drug-Resistant Gram-Negative Bacteria

Antibiotic resistance in bacteria poses a global health challenge, underscoring the need for strategies that restore the effectiveness of existing drugs. Here, we demonstrate that amphiphilic Janus nanoparticles (NPs), with separate polycationic and hydrophobic hemispheres, act as effective antibiotic adjuvants that synergistically enhance the activity of conventional antibiotics. Unlike uniformly cationic NPs, Janus NPs exhibited strong synergy with multiple antibiotics against <i>Acinetobacter baumannii</i>, including the multidrug-resistant clinical isolate <i>A. baumannii</i> A42-2. Embedding Janus NPs in agar gel provided a stable platform that reproducibly increased antibiotic susceptibility in various Gram-negative bacteria, including <i>A. baumannii</i> and highly motile species such as <i>Escherichia coli</i>. These findings demonstrate that amphiphilic Janus NPs can synergistically boost antibiotic activity and that embedding them in gels yields a stable platform for assessing their performance and potentially deploying them in future biomedical applications.