Antibacterial Activity of Amphiphilic Janus Nanoparticles Enhanced by Polycationic Ligands

The rapid rise of antibiotic resistance has become a critical global health concern, necessitating the development of alternative treatments, such as antibacterial nanoparticles (NPs). While the antibacterial potency of these NPs is known to depend highly on their surface chemistry, existing designs predominantly include NPs with uniform surface coatings. In this study, we present a distinctive approach to using the surface anisotropy of NPs to modulate their antibacterial efficacy. Specifically, we investigate the antibacterial properties of amphiphilic Janus nanoparticles (NPs), which display spatially separated hydrophobic and cationic ligands on opposing sides. By integrating experiments with molecular dynamics simulations, we unveil the crucial role of polycationic ligands in enhancing the interaction between Janus NPs and bacteria, ultimately leading to a significantly improved antibacterial potency. With hydrophobic and polycationic ligands spatially separated on a single NP surface, these amphiphilic Janus NPs effectively permeabilize the cell envelopes of both Gram-negative and Gram-positive bacteria. As a result, they inhibit bacterial growth at lower concentrations compared with NPs with uniform surface chemistry. Moreover, we demonstrate the versatility of the Janus NPs’ antibacterial activity across various types of polycationic ligands. Our findings provide a mechanistic understanding of the spatial arrangement of ligands as well as the molecular characteristics of ligands in modulating NP–bacteria interactions. This research underscores the potential of Janus NPs, a distinctive subgroup of nanoparticles characterized by their anisotropic surface chemistry, as a unique class of antibacterial materials.