Targeted delivery of oxaliplatin to colorectal cancer using the cancer-specific cell-penetrating peptide BR2

초록

Oxaliplatin is one of the main drugs used in chemotherapy to treat advanced colorectal cancer (CRC), but its effectiveness is limited by its weak cellular uptake, and poor targeting to cancer cells, which can lead to drug resistance and adverse effects in patients. To address these issues, we tested a cell-penetrating, cancer-specific peptide called BR2 as a new peptide-drug conjugate. We conjugated oxaliplatin with BR2 covalently using a heterobifunctional linker. The resulting conjugate (BR2-Oxal) was examined for in vitro and in vivo effectiveness against human colon cancer cells and tumors. Compared with the parent drug, the in vitro investigations showed selective cellular uptake of BR2-Oxal in cancer cells rather than in normal cells and a significantly greater reduction in colon cancer cell viability due to a higher ratio of apoptosis. We also found that BR2-Oxal exhibited a higher accumulation in tumors and greater tumor suppression than oxaliplatin in a xenograft mouse model, suggesting that BR2-Oxal was efficiently and specifically delivered to tumors in vivo. These findings indicate that using the BR2 peptide for the intracellular delivery of oxaliplatin is a promising drug-delivery strategy. This approach also has the potential to enhance the efficiency of oxaliplatin prodrugs or derivatives.

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