Brucea javanica derived exosome-like nanovesicles deliver miRNAs for cancer therapy

Triple-negative breast cancer (TNBC) is characterized by complex heterogeneity, high recurrence and metastasis rates, and short overall survival , owing to the lack of endocrine and targeted receptors, which necessitates chemotherapy as the major treatment regimen. Exosome-like nanovesicles derived from medicinal plants have shown great potential as novel biotherapeutics for cancer therapy by delivering their incorporated nucleic acids , especially microRNAs (miRNAs), to mammalian cells. In this study, we isolated exosome-like nanovesicles derived from B. javanica (BF-Exos) and investigated their influence and underlying molecular mechanisms in TNBC. We found that BF-Exos delivered 10 functional miRNAs to 4T1 cells, significantly retarding the growth and metastasis of 4T1 cells by regulating the PI3K/Akt/mTOR signaling pathway and promoting ROS/caspase-mediated apoptosis. Moreover, BF-Exos were shown to inhibit the secretion of vascular endothelial growth factor, contributing to anti-angiogenesis in the tumor microenvironment . In vivo, BF-Exos inhibited tumor growth, metastasis, and angiogenesis in breast tumor mouse models, while maintaining high biosafety. Overall, BF-Exos are considered promising nanoplatforms for the delivery of medicinal plant-derived nucleic acids , with great potential to be developed into novel biotherapeutics for the treatment of TNBC.

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