Cell-derived small extracellular vesicles have been exploited as potent drug vehicles. However, significant challenges hamper their clinical translation, including inefficient cytosolic delivery, poor target-specificity, low yield, and inconsistency in production. Here, we report a bioinspired material, engineered fusogen and targeting moiety co-functionalized cell-derived nanovesicle (CNV) called eFT-CNV, as a drug vehicle. We show that universal eFT-CNVs can be produced by extrusion of genetically modified donor cells with high yield and consistency. We demonstrate that bioinspired eFT-CNVs can efficiently and selectively bind to targets and trigger membrane fusion, fulfilling endo-lysosomal escape and cytosolic drug delivery. We find that, compared to counterparts, eFT-CNVs significantly improve the treatment efficacy of drugs acting on cytosolic targets. We believe that our bioinspired eFT-CNVs will be promising and powerful tools for nanomedicine and precision medicine.

细胞来源的小细胞外囊泡已被用作有效的药物载体。然而，重大挑战阻碍了它们的临床转化，包括胞质递送效率低、靶标特异性差、产量低和生产不一致。在这里，我们报告了一种仿生材料、工程融合剂和靶向部分共同功能化的细胞衍生纳米囊泡 (CNV)，称为 eFT-CNV，作为药物载体。我们证明，通用的 eFT-CNV 可以通过转基因供体细胞的挤出来生产，并且具有高产量和一致性。我们证明，仿生 eFT-CNV 可以有效、选择性地结合靶标并触发膜融合，实现内溶酶体逃逸和胞质药物递送。我们发现，与同类药物相比，eFT-CNV 显着提高了作用于细胞质靶点的药物的治疗效果。我们相信，我们的仿生 eFT-CNV 将成为纳米医学和精准医学的有前途且强大的工具。