Geng Tianjiao, Pan Patrick, Leung Euphemia, Chen Qi, Chamley Larry, Wu Zimei
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
Pharm Res. 2021 Feb;38(2):179-197. doi: 10.1007/s11095-021-02988-z. Epub 2021 Feb 18.
Extracellular vesicles (EVs) are a heterogeneous population of lipid bilayer membrane-enclosed vesicles and act like 'messages in a bottle' in cell-cell communication by transporting their cargoes to recipient cells. Small EVs (sEVs, < 200 nm) are highly researched recently and have been harnessed as novel delivery systems for the treatment of various diseases, including neurodegenerative disorders, cardiovascular diseases, and most importantly cancer primarily because of their non-immunogenicity, tissue penetration and cell-tropism. This review will first provide a comprehensive overview of sEVs regarding the current understanding on their properties, biogenesis, new classification by the ISEV, composition, as well as their roles in cancer development (thereby called "oncosomes"). The primary focus will be given to the current state of sEVs as natural nanocarriers for cancer drug delivery, the technologies and challenges involved in sEV isolation and characterization, therapeutic cargo loading, and surface modification to enhance tumor-targeting. We will also provide examples of sEV products under clinical trials. Furthermore, the current challenges as well as the advance in "sEV mimetics" to address some of the sEVs limitations is briefly discussed. We seek to advance our understanding of sEVs to unlock their full potential as superior drug delivery vehicles in cancer therapy.
细胞外囊泡（EVs）是脂质双分子膜包裹的异质性囊泡群体，在细胞间通讯中犹如“瓶中信”，通过将其携带的物质运输到受体细胞发挥作用。小细胞外囊泡（sEVs，<200 nm）近来受到广泛研究，并已被用作治疗多种疾病的新型递送系统，包括神经退行性疾病、心血管疾病，以及最重要的癌症，主要是因为它们具有非免疫原性、组织穿透性和细胞嗜性。本综述将首先全面概述小细胞外囊泡，内容涉及对其性质、生物发生、国际细胞外囊泡学会（ISEV）的新分类、组成，以及它们在癌症发展中的作用（因此被称为“癌小体”）的当前认识。主要关注点将是小细胞外囊泡作为癌症药物递送天然纳米载体的现状、小细胞外囊泡分离与表征、治疗性物质装载以及增强肿瘤靶向性的表面修饰所涉及的技术和挑战。我们还将提供正在进行临床试验的小细胞外囊泡产品实例。此外，还将简要讨论当前的挑战以及“小细胞外囊泡模拟物”在解决小细胞外囊泡某些局限性方面的进展。我们旨在增进对小细胞外囊泡的理解，以释放其在癌症治疗中作为卓越药物递送载体的全部潜力。
