Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles.

Autor: Wang, Lixue, Wang, Guosheng, Mao, Wenjun, Chen, Yundi, Rahman, Md. Mofizur, Zhu, Chuandong, Prisinzano, Peter M., Kong, Bo, Wang, Jing, Lee, Luke P., Wan, Yuan
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Zdroj: Nature Communications; 6/8/2023, Vol. 14 Issue 1, p1-12, 12p
Abstrakt: 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. Active targeting and cytosolic delivery of therapeutic payloads are challenging in small extracellular vesicle-based drug delivery systems. Here, the authors engineer fusogen and targeting moiety co-functionalized cell-derived nanovesicles, which can selectively bind to target cells and efficiently fulfill cytosolic delivery through membrane fusion. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index