细胞脱水能够大规模生产具有治疗功能的工程膜囊泡。
Cell dehydration enables massive production of engineered membrane vesicles with therapeutic functions.
发表日期:2024 Jul
作者:
Jie Liu, Tingting Shen, Yu Zhang, Xiaojian Wei, Yuting Bao, Rui Ai, Shaoju Gan, Dachi Wang, Xin Lai, Libo Zhao, Wei Zhou, Xiaohong Fang
来源:
Journal of Extracellular Vesicles
摘要:
细胞外囊泡(EV)已成为治疗不同疾病的有前途的生物材料。然而,迄今为止,仅报道了少数具有临床转化潜力的EV,并且其在生物安全控制条件下的大规模制备也有限。在这项研究中,我们描述了一种具有良好临床应用潜力的新型EV:脱水诱导的细胞外囊泡(DIMV)。 DIMV 是一种微米直径的细胞囊泡,与之前报道的细胞囊泡相比,它含有更多的生物活性分子,例如蛋白质和 RNA,但不含 DNA。 DIMV的制备非常简单,具有高度的生物安全性,并且蛋白质利用率比自然分泌的EV大约高600倍。其他实验证明了分离前或分离后 DIMV 修饰的可行性,包括基因编辑、核酸封装或表面锚定、大小调整。最后,在动物模型上,我们直接展示了 DIMV 的生物安全性和免疫原性,并研究了其作为肿瘤疫苗或药物载体在癌症治疗中的潜在应用。© 2024 作者。 《Journal of Extracellular Vesicles》由 Wiley periodicals LLC 代表国际细胞外囊泡学会出版。
Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types of EVs with clinical transformation potential have been reported to date, and their preparation on a large scale under biosafety-controlled conditions is limited. In this study, we characterize a novel type of EV with promising clinical application potential: dehydration-induced extracellular vesicles (DIMVs). DIMV is a type of micron-diameter cell vesicle that contains more bioactive molecules, such as proteins and RNA, but not DNA, than previously reported cell vesicles. The preparation of DIMV is extraordinarily straightforward, which possesses a high level of biosafety, and the protein utilization ratio is roughly 600 times greater than that of naturally secreted EVs. Additional experiments demonstrate the viability of pre- or post-isolation DIMV modification, including gene editing, nucleic acid encapsulation or surface anchoring, size adjustment. Finally, on animal models, we directly show the biosafety and immunogenicity of DIMV, and investigate its potential application as tumour vaccine or drug carrier in cancer treatment.© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.