Department of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
The Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA.
Nat Commun. 2023 Jun 8;14(1):3366. doi: 10.1038/s41467-023-39181-2.
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.
细胞衍生的小细胞外囊泡已被用作有效的药物载体。然而，其临床转化仍面临重大挑战，包括胞质内递送效率低、靶向特异性差、产量低以及生产不一致等。在这里，我们报告了一种受生物启发的材料，即融合蛋白和靶向部分共功能化的细胞衍生纳米囊泡（CNV），称为 eFT-CNV，可作为药物载体。我们表明，通过挤压经基因修饰的供体细胞可以高效率、高一致性地生产出通用的 eFT-CNV。我们证明了受生物启发的 eFT-CNV 可以有效地和选择性地与靶标结合并触发膜融合，实现内体/溶酶体逃逸和胞质内药物递送。我们发现，与对照物相比，eFT-CNV 显著提高了作用于胞质内靶标的药物的治疗效果。我们相信，我们受生物启发的 eFT-CNV 将成为纳米医学和精准医学的有前途和强大的工具。
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