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

Salmonella enterica serovar Typhimurium (S. Typhimurium) 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 S. Typhimurium 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 S. Typhimurium 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 S. Typhimurium. 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.