Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536, USA.
Int J Mol Sci. 2023 Oct 15;24(20):15206. doi: 10.3390/ijms242015206.
Extracellular vesicles (EVs) are small, membrane-bound vesicles used by cells to deliver biological cargo such as proteins, mRNA, and other biomolecules from one cell to another, thus inducing a specific response in the target cell and are a powerful method of cell to cell and organ to organ communication, especially during the pathogenesis of human disease. Thus, EVs may be utilized as prognostic and diagnostic biomarkers, but they also hold therapeutic potential just as mesenchymal stem cells have been used in therapeutics. However, unmodified EVs exhibit poor targeting efficacy, leading to the necessity of engineered EVS. To highlight the advantages and therapeutic promises of engineered EVs, in this review, we summarized the research progress on engineered EVs in the past ten years, especially in the past five years, and highlighted their potential applications in therapeutic development for human diseases. Compared to the existing stem cell-derived EV-based therapeutic strategies, engineered EVs show greater promise in clinical applications: First, engineered EVs mediate good targeting efficacy by exhibiting a targeting peptide that allows them to specifically target a specific organ or even cell type, thus avoiding accumulation in undesired locations and increasing the potency of the treatment. Second, engineered EVs can be artificially pre-loaded with any necessary biomolecular cargo or even therapeutic drugs to treat a variety of human diseases such as cancers, neurological diseases, and cardiovascular ailments. Further research is necessary to improve logistical challenges in large-scale engineered EV manufacturing, but current developments in engineered EVs prove promising to greatly improve therapeutic treatment for traditionally difficult to treat diseases.
细胞外囊泡 (EVs) 是一种小型的膜结合囊泡,细胞使用它来将生物货物(如蛋白质、mRNA 和其他生物分子)从一个细胞递送到另一个细胞,从而在靶细胞中诱导特定的反应,是细胞间和器官间通讯的一种强大方法,特别是在人类疾病的发病机制中。因此,EVs 可以用作预后和诊断的生物标志物,但它们也具有治疗潜力,正如间充质干细胞在治疗中被使用一样。然而,未经修饰的 EVs 表现出较差的靶向效果,因此需要对 EVs 进行工程化处理。为了突出工程化 EVs 的优势和治疗潜力,在这篇综述中,我们总结了过去十年,特别是过去五年中工程化 EVs 的研究进展,并强调了它们在人类疾病治疗开发中的潜在应用。与现有的基于干细胞衍生的 EV 治疗策略相比,工程化 EVs 在临床应用中显示出更大的潜力:首先,工程化 EVs 通过展示靶向肽来介导良好的靶向效果,使它们能够特异性地靶向特定的器官甚至细胞类型,从而避免在不需要的位置积累,提高治疗效果。其次,工程化 EVs 可以被人为地预先装载任何必要的生物分子货物甚至治疗药物,以治疗各种人类疾病,如癌症、神经疾病和心血管疾病。需要进一步研究来改善大规模工程化 EV 制造中的物流挑战,但工程化 EVs 的当前发展证明有望极大地改善传统上难以治疗的疾病的治疗效果。