Unveiling Janus Particle-Bacteria Interactions Towards Nano-Antibiotics Development

Multidrug-resistant bacteria pose a global threat to human health. To address this challenge, antibacterial nanoparticles (NPs) have been developed as a potential alternative to traditional antibiotics. These NPs can kill bacteria through mechanisms, such as DNA binding, generation of reactive oxygen species (ROS), and physical damage to bacterial cell wall, which are less likely to induce bacterial resistance compared to traditional antibiotics. However, due to the diverse nature of bacteria, there is a need to design antibacterial NPs that allow easy tuning of the NP surface chemistry for broad-spectrum antibiotic activity. In this study, we have successfully synthesized antimicrobial NPs by tuning the anisotropic surface chemistry. Specifically, we engineered anisotropic NPs with two distinct hemispheres, which are also known as Janus NPs. One side of the Janus NPs was coated with a hydrophobic ligand and the other with a cationic/hydrophilic polycationic ligand. The amphiphilic Janus NPs exhibited superior antibacterial properties compared to NPs with uniform surface chemistry, demonstrating effectiveness against both Gram-negative and Gram-positive bacteria. We revealed that the antibacterial mechanisms of Janus NPs include both physical damage to the bacterial cell wall and the generation of ROS. Further, we made an interesting discovery that the Janus NPs preferentially damage the poles of Escherichia coli in a curvature-dependent mechanism. These findings collectively not only underscore the potential of Janus NPs as a new type of nano-antibiotics against multi-drug resistant bacteria but also elucidate physical interactions driving the NP antibacterial activities.