Zheng Li-Ting, Yang Ge, Qu Feng
School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Se Pu. 2025 May;43(5):424-433. doi: 10.3724/SP.J.1123.2024.10029.
Exosomes play crucial intercellular-communication roles and regulate various cellular physiological processes. They are considered potential biomarkers for the early diagnosis of cancers and other diseases. Therefore, detecting and isolating exosomes with specific functions has significant clinical implications. Moreover, the development of low-cost, highly sensitive recognition elements for identifying exosomes is essential for advancing early disease diagnosis and treatment. Nucleic acid aptamers are single-stranded DNA or RNA molecules capable of specifically binding to targets and are produced through the systematic evolution of ligands by exponential enrichment (SELEX) technique. Such aptamers are highly stable, chemically synthesizable, exhibit high affinities and specificities, and are applicable to a broad range of targets, which endow them with unique advantages. Currently, aptamers that target exosomes have been used in a variety of research fields, including cell imaging, drug delivery, and disease diagnosis and treatment. However, selecting aptamers that precisely identify specific exosomes is significantly challenging owing to the complex structures of exosome and their heterogeneity. Consequently, obtaining high-performance aptamers requires efficient screening techniques. This review first summarizes the functions and selection strategies of key targets for exosome-aptamer screening. Furthermore, it outlines the main methods and techniques currently used to screen exosome aptamers, which includes five screening techniques: magnetic bead-SELEX, microfluidic-SELEX, nitrocellulose-SELEX, cell-SELEX, and capillary electrophoresis-SELEX. The separation principles, advantages, limitations, and the latest applications of these techniques are discussed in detail. The review finally addresses current challenges associated with selecting exosome aptamers and provides insight into future research directions.
外泌体在细胞间通讯中发挥着关键作用，并调节各种细胞生理过程。它们被认为是癌症和其他疾病早期诊断的潜在生物标志物。因此，检测和分离具有特定功能的外泌体具有重要的临床意义。此外，开发用于识别外泌体的低成本、高灵敏度识别元件对于推进疾病的早期诊断和治疗至关重要。核酸适体是能够特异性结合靶标的单链DNA或RNA分子，通过指数富集配体系统进化（SELEX）技术产生。这类适体高度稳定、可化学合成，具有高亲和力和特异性，适用于广泛的靶标，这赋予了它们独特的优势。目前，靶向外泌体的适体已被应用于包括细胞成像、药物递送以及疾病诊断和治疗在内的各种研究领域。然而，由于外泌体的复杂结构及其异质性，选择能够精确识别特定外泌体的适体具有重大挑战性。因此，获得高性能适体需要高效的筛选技术。本综述首先总结了外泌体适体筛选关键靶标的功能和选择策略。此外，还概述了目前用于筛选外泌体适体的主要方法和技术，包括五种筛选技术：磁珠SELEX、微流控SELEX、硝酸纤维素SELEX、细胞SELEX和毛细管电泳SELEX。详细讨论了这些技术的分离原理、优点、局限性及最新应用。综述最后探讨了当前选择外泌体适体所面临的挑战，并对未来的研究方向提供了见解。
