Raja Mohanakrishna, Ramamurthy Karthikeyan, Sudhakaran Gokul, Guru Ajay, Arockiaraj Jesu
Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulatur, Chengalpattu District, 603203, Tamil Nadu, India.
Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, 600077, Tamil Nadu, India.
Arch Microbiol. 2025 Apr 10;207(5):118. doi: 10.1007/s00203-025-04294-3.
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.
细胞外囊泡（EVs）是细胞产生的膜结合囊泡，通过传递DNA、RNA和蛋白质等不同内容物促进细胞间通讯。这些纳米大小的囊泡释放到细胞外空间，在正常和病理条件下均广泛存在。益生菌衍生的EVs可作为治疗性货物的纳米载体，特别是在酶替代疗法（ERT）中。用于溶酶体贮积症（LSDs）的传统ERT面临重大挑战，包括酶无法穿过血脑屏障（BBB）以及它们易被降解。研究表明，EVs可以将酶货物转运穿过BBB，准确地将它们递送至受LSDs影响的组织。益生菌EVs还具有免疫调节特性，在炎症条件下具有治疗益处。然而，它们在LSDs中递送缺陷酶的潜力仍不清楚。本综述讨论了在ERT中使用益生菌EVs进行靶向酶递送，以比其他外泌体更有效地治疗LSDs。这种新策略可最大限度地减少脱靶递送并增强免疫调节作用，使其比活益生菌更具优势。益生菌EVs通过调节免疫反应并跨越BBB等生物屏障递送酶，在治疗方法中显示出前景，特别是在治疗LSDs和炎症性疾病方面。未来的研究应优化生产，设计靶向疗法，并通过临床试验确认安全性和有效性。将研究扩展到包括多种益生菌菌株可能会发现新的治疗应用，提高它们的多功能性和有效性。
