细胞外囊泡作为穿越血脑屏障治疗溶酶体贮积病的工具
Extracellular Vesicles as Tools for Crossing the Blood-Brain Barrier to Treat Lysosomal Storage Diseases.
作者信息
Lerussi Giovanni, Villagrasa-Araya Verónica, Moltó-Abad Marc, Del Toro Mireia, Pintos-Morell Guillem, Seras-Franzoso Joaquin, Abasolo Ibane
机构信息
Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT), Vall d'Hebron Institute of Research (VHIR), 08035 Barcelona, Spain.
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 08035 Barcelona, Spain.
出版信息
Life (Basel). 2025 Jan 9;15(1):70. doi: 10.3390/life15010070.
Extracellular vesicles (EVs) are nanosized, membrane-bound structures that have emerged as promising tools for drug delivery, especially in the treatment of lysosomal storage disorders (LSDs) with central nervous system (CNS) involvement. This review highlights the unique properties of EVs, such as their biocompatibility, capacity to cross the blood-brain barrier (BBB), and potential for therapeutic cargo loading, including that of enzymes and genetic material. Current therapies for LSDs, like enzyme replacement therapy (ERT), often fail to address neurological symptoms due to their inability to cross the BBB. EVs offer a viable alternative, allowing for targeted delivery to the CNS and improving therapeutic outcomes. We discuss recent advancements in the engineering and modification of EVs to enhance targeting, circulation time and cargo stability, and provide a detailed overview of their application in LSDs, such as Gaucher and Fabry diseases, and Sanfilippo syndrome. Despite their potential, challenges remain in scaling production, ensuring isolation purity, and meeting regulatory requirements. Future developments will focus on overcoming these barriers, paving the way for the clinical translation of EV-based therapies in LSDs and other CNS disorders.
细胞外囊泡(EVs)是纳米级的膜结合结构,已成为有前景的药物递送工具,特别是在治疗涉及中枢神经系统(CNS)的溶酶体贮积症(LSDs)方面。本综述强调了EVs的独特特性,如它们的生物相容性、穿越血脑屏障(BBB)的能力以及装载治疗性货物(包括酶和遗传物质)的潜力。目前治疗LSDs的方法,如酶替代疗法(ERT),由于无法穿越BBB,往往无法解决神经症状。EVs提供了一种可行的替代方案,能够靶向递送至CNS并改善治疗效果。我们讨论了EVs在工程改造方面的最新进展,以增强靶向性、循环时间和货物稳定性,并详细概述了它们在LSDs(如戈谢病和法布里病以及桑菲利普综合征)中的应用。尽管它们具有潜力,但在扩大生产规模、确保分离纯度和满足监管要求方面仍存在挑战。未来的发展将集中在克服这些障碍,为基于EVs的疗法在LSDs和其他CNS疾病中的临床转化铺平道路。