Laboratory of Genetic Technologies, Martsinovsky Institute of Medical Parasitology, Tropical and Vector-Borne Diseases, First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.
Division of Biotechnology, Sirius University of Science and Technology, 354340 Sochi, Russia.
Int J Mol Sci. 2024 Sep 27;25(19):10401. doi: 10.3390/ijms251910401.
Extracellular vesicles (EVs) are natural carriers of biomolecules that play a crucial role in cell-to-cell communication and tissue homeostasis under normal and pathological conditions, including inflammatory diseases and cancer. Since the discovery of the pro-regenerative and immune-modulating properties of EVs, EV-based therapeutics have entered clinical trials for conditions such as myocardial infarction and autoimmune diseases, among others. Due to their unique advantages-such as superior bioavailability, substantial packaging capacity, and the ability to traverse biological barriers-EVs are regarded as a promising platform for targeted drug delivery. However, achieving a sufficient accumulation of therapeutic agents at the target site necessitates a larger quantity of EVs per dose compared to using EVs as standalone drugs. This challenge can be addressed by administering larger doses of EVs, increasing the drug dosage per administration, or enhancing the selective accumulation of EVs at target cells. In this review, we will discuss methods to improve the isolation and purification of EVs, approaches to enhance cargo packaging-including proteins, RNAs, and small-molecule drugs-and technologies for displaying targeting ligands on the surface of EVs to facilitate improved targeting. Ultimately, this guide can be applied to the development of novel classes of EV-based therapeutics and to overcoming existing technological challenges.
细胞外囊泡 (EVs) 是生物分子的天然载体，在正常和病理条件下（包括炎症性疾病和癌症），对于细胞间通讯和组织稳态发挥着至关重要的作用。自发现 EV 具有促再生和免疫调节特性以来，基于 EV 的疗法已进入临床试验，用于治疗心肌梗死和自身免疫性疾病等多种疾病。由于其独特的优势，如较高的生物利用度、大量的包装能力以及穿越生物屏障的能力，EV 被视为靶向药物递送的有前途的平台。然而，与将 EV 作为单一药物使用相比，要实现治疗剂在靶部位的充分积累，需要每剂量使用更多数量的 EV。通过给予更大剂量的 EV、增加每次给药的药物剂量或增强 EV 在靶细胞上的选择性积累，可以解决这一挑战。在这篇综述中，我们将讨论改进 EV 分离和纯化的方法、增强货物包装的方法（包括蛋白质、RNA 和小分子药物）以及在 EV 表面展示靶向配体的技术，以促进更好的靶向性。最终，本指南可应用于新型 EV 治疗药物的开发，并克服现有技术挑战。
