Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Victoria, 3086, Australia.
Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, 9220, Denmark.
Proteomics. 2019 Apr;19(8):e1800161. doi: 10.1002/pmic.201800161. Epub 2019 Apr 3.
Issues associated with upscaling exosome production for therapeutic use may be overcome through utilizing artificial exosomes. Cell-derived mimetic nanovesicles (M-NVs) are a potentially promising alternative to exosomes for clinical applicability, demonstrating higher yield without incumbent production and isolation issues. Although several studies have shown that M-NVs have similar morphology, size and therapeutic potential compared to exosomes, comprehensive characterization and to what extent M-NVs components mimic exosomes remain elusive. M-NVs were generated through the extrusion of cells and proteomic profiling demonstrated an enrichment of proteins associated with membrane and cytosolic components. The proteomic data herein reveal a subset of proteins that are highly abundant in M-NVs in comparison to exosomes. M-NVs contain proteins that largely represent the parental cell proteome, whereas the profile of exosomal proteins highlight their endosomally derived origin. This advantage of M-NVs alleviates the necessity of endosomal sorting of endogenous therapeutic proteins or RNA into exosomes. This study also highlights differences in protein post-translational modifications among M-NVs, as distinct from exosomes. Overall this study provides key insights into defining the proteome composition of M-NVs as a distinct from exosomes, and the potential advantage of M-NVs as an alternative nanocarrier when spontaneous endosomal sorting of therapeutics are limited.
用于治疗用途的外泌体生产放大相关问题可以通过利用人工外泌体来克服。细胞衍生的模拟纳米囊泡（M-NVs）是外泌体在临床应用中具有潜在应用前景的替代品，其产量更高，不存在当前生产和分离的问题。尽管几项研究表明 M-NVs 在形态、大小和治疗潜力方面与外泌体相似，但对 M-NVs 成分与外泌体的模拟程度的全面表征仍然难以捉摸。M-NVs 通过细胞挤压产生，蛋白质组学分析表明，M-NVs 中富含与膜和细胞质成分相关的蛋白质。本文中的蛋白质组学数据揭示了与外泌体相比，M-NVs 中高度丰富的蛋白质子集。M-NVs 包含的蛋白质在很大程度上代表了亲本细胞的蛋白质组，而外泌体蛋白的特征则突出了它们的内体起源。M-NVs 的这一优势减轻了将内源性治疗蛋白或 RNA 内体分拣到外泌体中的必要性。本研究还强调了 M-NVs 中蛋白质翻译后修饰的差异，与外泌体不同。总的来说，这项研究为定义 M-NVs 的蛋白质组组成提供了重要的见解，M-NVs 作为一种替代纳米载体具有潜在的优势，特别是在治疗药物的内体分拣受到限制时。
