Bacterial Outer Membrane Vesicles: From Physics to Clinical

ABSTRACT Bacterial outer membrane vesicles (OMVs) are nanoscale vesicular structures naturally produced by Gram‐negative bacteria during growth. These vesicles encapsulate a diverse array of bioactive molecules, including proteins, nucleic acids, and lipopolysaccharide, contributing to a range of bacterial processes such as toxin delivery, horizontal gene transfer, and biofilm formation. OMVs play crucial roles in bacterial pathogenesis and host immune modulation, and their presence is implicated in a variety of clinical conditions affecting the respiratory, gastrointestinal, immune, cardiovascular, and urinary systems. The unique properties of OMVs offer promising avenues for clinical translation, including their use as vaccines (against bacterial, viral, parasitic, and tumor‐associated), diagnostic tools (for bioimaging and molecular diagnostics), drug delivery vehicles (for antibiotics, anti‐cancer therapeutics, and nucleic acids) and regenerative medicine. However, several challenges hinder the widespread clinical adoption of OMVs, including heterogeneity in composition depending on growth conditions, incompletely understood mechanisms of cargo loading and release, inherent immunogenicity and potential toxicity, and limitations in scalable production. This review aims to provide a comprehensive overview of OMVs biogenesis, composition, function, and association with human disease, while also exploring current challenges and future development directions for clinical application.