Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Animal Physiology and Immunology, TUM School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
Adv Drug Deliv Rev. 2021 Jul;174:348-368. doi: 10.1016/j.addr.2021.04.027. Epub 2021 May 5.
Extracellular vesicles (EVs) are membranous nanovesicles secreted from living cells, shuttling macromolecules in intercellular communication and potentially possessing intrinsic therapeutic activity. Due to their stability, low immunogenicity, and inherent interaction with recipient cells, EVs also hold great promise as drug delivery vehicles. Indeed, they have been used to deliver nucleic acids, proteins, and small molecules in preclinical investigations. Furthermore, EV-based drugs have entered early clinical trials for cancer or neurodegenerative diseases. Despite their appeal as delivery vectors, however, EV-based drug delivery progress has been hampered by heterogeneity of sample types and methods as well as a persistent lack of standardization, validation, and comprehensive reporting. This review highlights specific requirements for EVs in drug delivery and describes the most pertinent approaches for separation and characterization. Despite residual uncertainties related to pharmacodynamics, pharmacokinetics, and potential off-target effects, clinical-grade, high-potency EV drugs might be achievable through GMP-compliant workflows in a highly standardized environment.
细胞外囊泡 (EVs) 是从活细胞分泌的膜性纳米囊泡，在细胞间通讯中穿梭传递大分子物质，并具有潜在的内在治疗活性。由于其稳定性、低免疫原性和与受体细胞的固有相互作用，EVs 也有望成为药物递送载体。事实上，它们已被用于临床前研究中递送核酸、蛋白质和小分子。此外，基于 EV 的药物已进入癌症或神经退行性疾病的早期临床试验。然而，尽管它们作为递送载体具有吸引力，但由于样本类型和方法的异质性以及持续缺乏标准化、验证和全面报告，EV 为基础的药物输送进展受到了阻碍。本综述强调了药物输送中对 EV 的特定要求，并描述了最相关的分离和表征方法。尽管与药效学、药代动力学和潜在的脱靶效应相关的残余不确定性，但通过符合 GMP 的工作流程在高度标准化的环境中可能实现临床级、高效力的 EV 药物。
