Maximizing Oxaliplatin's Impact on EGFR+ Colorectal Cancer Through Targeted Extracellular Vesicles

Abstract

Purpose: To investigate the ability of extracellular vesicles (EVs) to deliver oxaliplatin to epidermal growth factor receptor (EGFR+) colorectal cancer cells and increase oxaliplatin’s cytotoxicity. Method: Oxaliplatin was passively loaded into a stable cell line expressing cetuximab in membranes. EVs were collected and characterized for size, and their ability to target EGFR+ cells was tested. Cytotoxicity experiments were performed, and a xenograft cancer animal model was used to confirm the specific accumulation of oxaliplatin-loaded EVs with cetuximab-expressing membranes in EGFR+ cells. Results: EVs with cetuximab-expressing membranes were successfully produced and used to encapsulate oxaliplatin, resulting in consistently sized oxaliplatin-loaded EVs with cetuximab-expressing membranes. The oxaliplatin-loaded EVs with cetuximab-expressing membranes were specifically internalized by EGFR+ cells, leading to significant cytotoxic effects on these cells. In the animal model, the oxaliplatin-loaded EVs with cetuximab-expressing membranes accumulated specifically in EGFR+ cells and significantly enhanced oxaliplatin’s therapeutic efficacy against EGFR+ cancer cells. Conclusion: EVs with membrane-expressed bioactive molecules are a promising strategy for delivering therapeutic agents to EGFR+ colorectal cancer cells.