细胞外囊泡（EV）已成为基于核酸的治疗的潜在递送载体，但与其大规模生产和货物装载效率相关的挑战限制了其治疗潜力。为了解决这些问题，我们开发了一种新颖的“冲击波细胞外囊泡工程技术”(SWEET)，作为一种非遗传、可扩展的制造策略，使用冲击波 (SW) 将 siRNA 封装在 EV 中。在这里，我们描述了使用 SWEET 平台将大量 KRASG12C 靶向 siRNA 高效地加载到小型牛乳源 EV（sBMEV）中。装载 siRNA 的 sBMEV 有效沉默癌细胞中致癌的 KRASG12C 表达；当在非小细胞肺癌异种移植小鼠模型中静脉注射时，它们抑制了肿瘤生长。我们的研究证明了 SWEET 平台作为一种新方法的潜力，可以大规模生产载货电动汽车，用于广泛的治疗应用。© 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 a potential delivery vehicle for nucleic-acid-based therapeutics, but challenges related to their large-scale production and cargo-loading efficiency have limited their therapeutic potential. To address these issues, we developed a novel "shock wave extracellular vesicles engineering technology" (SWEET) as a non-genetic, scalable manufacturing strategy that uses shock waves (SWs) to encapsulate siRNAs in EVs. Here, we describe the use of the SWEET platform to load large quantities of KRASG12C-targeting siRNA into small bovine-milk-derived EVs (sBMEVs), with high efficiency. The siRNA-loaded sBMEVs effectively silenced oncogenic KRASG12C expression in cancer cells; they inhibited tumour growth when administered intravenously in a non-small cell lung cancer xenograft mouse model. Our study demonstrates the potential for the SWEET platform to serve as a novel method that allows large-scale production of cargo-loaded EVs for use in a wide range of therapeutic applications.© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.