College of Biomedical Engineering, Sichuan University, Chengdu 610065, China.
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China.
ACS Appl Mater Interfaces. 2023 Nov 22;15(46):53859-53870. doi: 10.1021/acsami.3c13845. Epub 2023 Nov 1.
Cancer-derived extracellular vesicles (EVs) have shown great potential in the field of cancer metastasis research. However, inefficient EV biofabrication has become a barrier to large-scale research on cancer-derived EVs. Here, we presented a novel method to enhance the biofabrication of cancer-derived EVs via audible acoustic wave (AAW), which yielded mechanical stimuli, including surface acoustic pressure and surface stress. Compared to EV yield in conventional static culture, AAW increased the number of cancer-derived EVs by up to 2.5-folds within 3 days. Furthermore, cancer-derived EVs under AAW stimulation exhibited morphology, size, and zeta potential comparable to EVs generated in conventional static culture, and more importantly, they showed the capability to promote cancer cell migration and invasion under both 2D and 3D culture conditions. Additionally, the elevation in EV biofabrication correlated with the activation of the ESCRT pathway and upregulation of membrane fusion-associated proteins (RAB family, SNARE family, RHO family) in response to AAW stimulation. We believe that AAW represents an attractive approach to achieving high-quantity and high-quality production of EVs and that it has the potential to enhance EV biofabrication from other cell types, thereby facilitating EV-based scientific and translational research.
癌症来源的细胞外囊泡（EVs）在癌症转移研究领域显示出巨大的潜力。然而，EV 的生物制造效率低下已成为癌症来源的 EV 大规模研究的障碍。在这里，我们提出了一种通过可听声波（AAW）增强癌症来源的 EV 生物制造的新方法，该方法产生了包括表面声压和表面应力在内的机械刺激。与传统静态培养中的 EV 产量相比，AAW 在 3 天内将癌症来源的 EV 数量增加了高达 2.5 倍。此外，在 AAW 刺激下的癌症来源的 EV 表现出与在传统静态培养中产生的 EV 相似的形态、大小和 ζ 电位，更重要的是，它们在 2D 和 3D 培养条件下表现出促进癌细胞迁移和侵袭的能力。此外，EV 生物制造的增加与 ESCRT 途径的激活以及膜融合相关蛋白（RAB 家族、SNARE 家族、RHO 家族）的上调相关，以响应 AAW 刺激。我们相信，AAW 是实现 EV 高产量和高质量生产的有吸引力的方法，并且有可能增强其他细胞类型的 EV 生物制造，从而促进基于 EV 的科学和转化研究。
