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

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.To treat epidermal growth factor receptor (EGFR) expressing solid tumors, we established oxaliplatin-loaded milk EV conjugated with GE11 peptide (GE11Milk EVoxal), which has a high affinity to EGFR and assessed their anti-cancer effect in vitro and in vivo.Drug-loaded GE11Milk EVoxal showed significantly higher incorporation into EGFR expressing cancer cells compared with milk EV without GE11 conjugation (Milk EVoxal), leading to apoptosis of cancer cells. GE11Milk EVoxal also inhibited cell viability compared to milk EVoxal or oxaliplatin alone. In colorectal cancer xenograft murine model, GE11Milk EVoxal showed the maximum therapeutic effect on tumor progression. These findings indicate that GE11Milk EVoxal suppresses EGFR expressing cancer through GE11 peptide-mediated EGFR targeting and subsequently anti-cancer drug delivery.Anti-cancer drug-loaded engineered milk EVs might be a novel therapeutic approach for treating patients with EGFR expressing solid tumors.