Engineered Bacterial Extracellular Vesicles: Developments, Challenges, and Opportunities

The abundant microbe-associated molecular patterns (MAMPs) and nanoscale structures of bacterial extracellular vesicles (bEVs) collectively facilitate their versatile biological activities. Building on these inherent properties, engineering methods encompassing physical, chemical, and genetic modifications have been strategically employed to enhance the functional diversity of bEVs. Therefore, bEVs are being explored as innovative and promising platforms for developing immunotherapeutic strategies targeting diverse pathological states. To establish a foundational understanding of bEVs, we first summarized their biogenesis, classification, structures and biomolecular constituents of bEVs. This review discusses techniques for bEV production and modification and explores the immunological characteristics and effects of engineered bEVs, along with their biomedical applications. Special attention is devoted to advanced engineering approaches and outlining the challenges and emerging avenues in the development of engineered bEVs. This review aims to systematically construct an evidence-based and comprehensive framework that promotes translational optimization and clinical implementation of engineered bEVs, thereby maximizing their application potential in the biomedical field.