Extracellular vesicles in antimicrobial therapy: Advances, challenges and perspectives

The escalating crisis of antimicrobial resistance (AMR) has underscored the imperative for innovative therapeutic strategies to combat multidrug-resistant (MDR) pathogens. Extracellular vesicles (EVs) have emerged as a revolutionary platform in antimicrobial therapy due to their intrinsic biocompatibility, precise targeting capabilities, and immunomodulatory functions. This review provides a comprehensive analysis of the origin, biogenesis, isolation, characterization techniques, and cutting-edge applications of EVs. We emphasize the integration of nanotechnology and EVs engineering strategies-such as antibiotic delivery, membrane coating, membrane fusion, and intelligent drug-loading technologies optimize vesicle targeting, stability, and controlled release, thereby achieving synergistic antimicrobial effects. Despite their promising potential in vaccine development and infection diagnostics, significant challenges remain in scalable production, heterogeneity control, pharmacokinetics, and clinical translation. Moreover, we propose multidisciplinary innovations, including EVs-antimicrobial combination, smart response therapies, personalized therapies, and digitalization and machine learning to expedite the transition of EVs from bench to bedside. By bridging bioengineering and nanotechnology, EVs hold the potential to redefine antimicrobial treatment paradigms, offering sustainable defense strategies for the post-antibiotic era. • Introduces extracellular vesicles biogenesis, isolation methods, and biological source differences in antimicrobial delivery. • Reviews antimicrobial mechanisms and applications of mammalian/bacterial extracellular vesicles. • Discusses the challenges and future directions of extracellular vesicles in antimicrobial applications.