Biotechnological application of Escherichia coli outer membrane vesicles for the delivery of Myristica fragrans phytochemicals in pancreatic cancer therapy

Bacterial outer membrane vesicles (OMVs) are emerging as natural nanocarriers for cancer therapy due to their ability to deliver bioactive molecules and to penetrate the tumor microenvironment. This study investigated the combined effects of Escherichia coli-derived OMVs and Myristica fragrans extract on pancreatic ductal adenocarcinoma (PDAC) cells. OMVs (50 µg/mL) and M. fragrans extract (IC₅₀: 25 µg/mL) significantly reduced PANC-1 cell viability and increased LDH release after 24 h of treatment (p < 0.01). The combination treatment induced oxidative stress, evidenced by increased total oxidant status and decreased antioxidant capacity. Molecular analysis showed upregulation of PTEN expression, reduced phosphorylated AKT levels, and an increased IL-1β/IL-10 ratio. These changes elevated the Bax/Bcl-2 ratio and activated caspase-3, indicating induction of apoptosis (p < 0.01). Our findings suggest that OMVs can effectively deliver M. fragrans phytochemicals to cancer cells, modulating oxidative balance and triggering apoptosis through the PTEN/AKT signaling pathway. This study provides preclinical evidence that combinations of microbial vesicles and plant extracts may enhance therapeutic efficacy against PDAC.