Inhibitory Effect of Oxaliplatin-loaded Engineered Milk Extracellular Vesicles on Tumor Progression
Gyeongyun Go, Hee Jung Park, Jun Hee Lee, Chul Won Yun, Sang Hun Lee
Abstract
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 (<sup>GE11</sup>Milk EV<sub>oxal</sub>), which has a high affinity to EGFR and assessed their anti-cancer effect in vitro and in vivo. Results: Drug-loaded <sup>GE11</sup>Milk EV<sub>oxal</sub> showed significantly higher incorporation into EGFR expressing cancer cells compared with milk EV without GE11 conjugation (Milk EV<sub>oxal</sub>), leading to apoptosis of cancer cells. <sup>GE11</sup>Milk EV<sub>oxal</sub> also inhibited cell viability compared to milk EV<sub>oxal</sub> or oxaliplatin alone. In colorectal cancer xenograft murine model, <sup>GE11</sup>Milk EV<sub>oxal</sub> showed the maximum therapeutic effect on tumor progression. These findings indicate that <sup>GE11</sup>Milk EV<sub>oxal</sub> 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.