Bacterial extracellular vesicles (Outer Membrane Vesicles): Biogenesis, engineering, and applications in drug delivery and vaccines

Bacterial extracellular vesicles, particularly outer membrane vesicles (OMVs), have emerged as promising nanotechnological platforms with diverse applications in biotechnology and medicine. These naturally occurring nanostructures, released by Gram-negative bacteria, are spherical proteo-liposomes ranging from 20 to 400 nm in diameter. OMVs contain lipopolysaccharides, membrane proteins, periplasmic proteins, and nucleic acids, making them ideal candidates for vaccine development and drug delivery systems. Recent advances in genetic engineering have enabled the development of hypervesiculating bacterial strains and innovative cargo loading strategies, significantly enhancing their therapeutic potential. This review comprehensively examines the biogenesis mechanisms of OMVs, genetic engineering approaches for their modification, and their applications as vaccine platforms and drug delivery vehicles. We discuss the successful implementation of OMV-based vaccines such as Bexsero for meningococcal disease and explore emerging applications in antibiotic and anticancer drug delivery. Furthermore, we address critical challenges in scale-up production, purification methodologies, and regulatory considerations that must be overcome for widespread clinical translation.