Emerging bacterial membrane vesicles from microbial messengers to therapeutic nanocarriers

Bacterial membrane vesicles (BMVs) are nanoscale vesicles that are naturally released by bacteria into the extracellular environment. By retaining the bacterium's membrane and luminal cargo, BMVs represent natural nanocarriers and long-distance messengers capable of influencing human health and disease progression. Depending on the bacterial species of origin, BMVs present important transport roles by carrying diverse native molecular cargo, protecting luminal cargo from degradation, promoting intracellular delivery and cytosolic release, crossing biological barriers, and mediating interactions with host cells. Recently, engineering strategies have emerged to harness these natural nanocarriers for the improved delivery of a wide range of therapeutic cargos, including proteins, antigens, nucleic acids, oncolytic viruses, polymers, and nanoparticles. These engineering strategies include genetic engineering, encapsulation, surface modification, and detoxification methods. Together, these strategies provide features including superior loading efficiency, targeted delivery, controlled release, longer circulation time, and multi-composite delivery approaches. This review discusses BMVs as versatile, multi-functional, and bio-active delivery vehicles along with current preparation methods, delivery routes, engineering strategies, highlighting unique features and challenges for translation.