Inhibitory Effect of Oxaliplatin-loaded Engineered Milk Extracellular Vesicles on Tumor Progression

Background/Aim: Anti-cancer chemotherapy is an effective therapeutic approach. Milk extracellular vesicles (EVs) loaded with chemotherapeutics have a potential anticancer effect by acting as a drug delivery system. Thus, our study aimed to explore the effect of engineered milk extracellular vesicles. Materials and Methods: To treat epidermal growth factor receptor (EGFR) expressing solid tumors, we established oxaliplatin-loaded milk EV conjugated with GE11 peptide (^GE11Milk EV_oxal), which has a high affinity to EGFR and assessed their anti-cancer effect in vitro and in vivo. Results: Drug-loaded ^GE11Milk EV_oxal showed significantly higher incorporation into EGFR expressing cancer cells compared with milk EV without GE11 conjugation (Milk EV_oxal), leading to apoptosis of cancer cells. ^GE11Milk EV_oxal also inhibited cell viability compared to milk EV_oxal or oxaliplatin alone. In colorectal cancer xenograft murine model, ^GE11Milk EV_oxal showed the maximum therapeutic effect on tumor progression. These findings indicate that ^GE11Milk EV_oxal suppresses EGFR expressing cancer through GE11 peptide-mediated EGFR targeting and subsequently anti-cancer drug delivery. Conclusion: Anti-cancer drug-loaded engineered milk EVs might be a novel therapeutic approach for treating patients with EGFR expressing solid tumors.