Microbe-Derived Extracellular Vesicles as Carriers for Doxorubicin Delivery to Colorectal Cancer Cells

<b>Background/Objectives:</b> Microbe-derived extracellular vesicles (MEVs) provide a biocompatible, naturally derived platform for drug delivery. <b>Methods:</b> We encapsulated doxorubicin in <i>Lactobacillus plantarum</i>-derived EVs and evaluated their ability at delivering doxorubicin to colorectal cancer cells in vitro. Endocytosis inhibitors were used to investigate the mechanisms by which the MEVs entered the cells. <b>Results:</b> The MEVs maintained structural stability under physiological conditions. Cellular internalization of doxorubicin-loaded MEVs involve clathrin/caveolae-dependent endocytosis, and dynamin- and clathrin-mediated pathways. <b>Conclusions:</b> These findings highlight the role of the microbe-cancer cell biointerface in mediating drug uptake and enabling intracellular delivery. The study supports the potential of MEVs as nanocarriers for anticancer drugs and provides mechanistic insights into the intracellular trafficking pathways that influence drug activity.