Exosomes are nanosized extracellular vesicles secreted by various cells, including natural killer (NK) cells, and are known for their low toxicity, high permeability, biocompatibility, and strong targeting ability. NK cell-derived exosomes (NK-exos) contain cytotoxic proteins that enhance tumor-targeting efficiency, making them suitable for treating solid tumors such as hepatocellular carcinoma (HCC). Despite their potential in drug delivery, the mechanisms of drug-loaded NK-exos, particularly those loaded with doxorubicin (NK-exos-Dox), remain unclear in HCC. This study explored the anti-tumor effects of NK-exos-Dox against Hep3B cells . NK-exos-Dox expressed exosome markers (CD9 and CD63) and cytotoxic proteins (granzyme B and perforin) and measured 170-220 nm in size. Compared to NK-exos, NK-exos-Dox enhanced cytotoxicity and apoptosis in Hep3B cells by upregulating pro-apoptotic proteins (Bax, cytochrome c, cleaved caspase 3, and cleaved PARP) and inhibiting the anti-apoptotic protein (Bcl-2). These findings suggest that NK-exos-Dox significantly boost anti-tumor effects by activating specific cytotoxic molecules, offering promising therapeutic opportunities for solid tumor treatment, including HCC.
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