Modification of Silver-Loaded Biodegradable Polymer Nanoparticles with Bacterial Membrane Vesicles for Treating Intracellular Bacterial Infections

<i>Salmonella enterica</i> serovar Typhimurium (<i>S</i>. <i>Typhimurium</i>) is an intracellular pathogen capable of surviving and replicating within macrophages, which causes foodborne diseases such as gastroenteritis. To develop a strategy against intracellular bacteria in macrophages, we designed silver-loaded biodegradable polymer nanoparticles functionalized with <i>S</i>. <i>Typhimurium</i> membrane vesicles (MVs). Silver nanoparticles (Ag NPs) were initially encapsulated within biodegradable poly(lactic-co-glycolic) nanoparticles (Ag-P NPs), which were then surface-modified with polyethyleneimine to form Ag-PP NPs. These were subsequently fused with <i>S. Typhimurium</i> MVs via a sonication method to generate Ag-PP@MV NPs. The resulting MV-coated nanoparticles displayed a similar protein profile to that of native MVs and exhibited antibacterial activity against intracellular <i>S</i>. <i>Typhimurium</i>. Notably, the enhanced cellular uptake of the MV-modified NPs contributed to their intracellular bactericidal efficacy. This study highlights MV modification as a promising strategy to improve NP delivery to macrophages for treating persistent intracellular infections.