A Nanocomposite with Extracellular Vesicles from Lactobacillus paracasei as a Bioinspired Nanoantibiotic Targeting Staphylococcus aureus

The utilization of biomimetic materials that merge functional nanoparticles (NPs) with a cell-derived nanosized membrane is a state-of-the-art approach to harnessing cellular properties for biomedical applications. However, the development of biocompatible and species-selective biomimetic agents against hazardous pathogens threatening human health is still in its early stages. Herein, we report the synthesis and functional analysis of a novel nanoplatform in which a PEGylated MoS2-ZnO (MZ) nanocomposite was cloaked with a generally regarded as safe (GRAS)-grade Lactobacillus paracasei-derived extracellular vesicle (LPEV) for MZ-LPEV nanocomposite and evaluated its activity against Staphylococcus aureus. The MZ nanocomposite was characterized via X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy. The coating of MZ with LPEV was confirmed through nanoparticle tracking analysis and zeta potential measurements. MZ-LPEV exhibited 5- to 20-fold higher antibacterial activity than that of ZO NPs and MZ nanocomposite against S. aureus. Reactive oxygen species (ROS) production and bacterial membrane disruption were confirmed as antibacterial mechanisms of MZ-LPEV. Finally, MZ-LPEV exhibited enhanced biocompatibility and selectivity for S. aureus. All our results showed that LPEV could be utilized for developing synergistic nanoantibiotics against S. aureus.