Exploring the potential of bacterial-derived EVs for targeted enzyme replacement therapy: mechanisms, applications,...

Extracellular vesicles (EVs) are membrane-bound vesicles produced by cells which promote intercellular communication by delivering different contents such as DNA, RNA, and proteins. These vesicles, nano-sized and released into the extracellular space, are present everywhere under both normal and pathological conditions. Probiotic-derived EVs can serve as nanocarriers for therapeutic cargo, particularly in enzyme replacement therapy (ERT). Traditional ERT for lysosomal storage diseases (LSDs) faces significant challenges, including the inability of enzymes to cross the blood-brain barrier (BBB) and their susceptibility to degradation. Studies show EVs can transport enzyme cargoes across the BBB, accurately delivering them to tissues affected by LSDs. Probiotic EVs also possess immunomodulatory properties, providing therapeutic benefits in inflammatory conditions. However, their potential for delivering deficient enzymes in LSDs remains unclear. This review discusses using probiotic EVs in ERT for targeted enzyme delivery to treat LSDs more efficiently than other exosomes. This novel strategy minimizes off-target delivery and enhances immunomodulatory effects, making it more advantageous than live probiotic bacteria. Probiotic EVs show promise for therapeutic approaches, especially in treating LSDs and inflammatory diseases, by modulating immune responses and delivering enzymes across biological barriers like the BBB. Future research should optimize production, engineer targeted therapies, and confirm safety and efficacy through clinical trials. Expanding studies to include diverse probiotic strains could uncover new therapeutic applications, enhancing their versatility and effectiveness.