Aim: To investigate the potential of PNC27 peptide, 12-26 of p53 with high affinity for HDM2 protein, as targeting ligand for Doxil to improve its antitumor activity.
Materials & methods: Doxil postinserted with 25, 50, 100 and 200 PNC27 peptides per liposome. Flow cytometry and confocal analysis were performed on C26 colon carcinoma (HDM2 positive) and B16F0 melanoma (HDM2 negative) cells. In vivo studies were performed on BALB/c mice bearing C26 and C57BL/6 mice bearing B16F0 tumor models.
Results: PNC27-Doxil showed significant cellular uptake and cytotoxicity in C26 cells compared with Doxil. PNC27-Doxil (100 PNC27 peptide) significantly improved therapeutic efficacy of Doxil without compromising its biodistribution in C26 tumor. However, these results were not observed in B16F0 cells.
Conclusion: PNC27 is a promising targeting ligand for Doxil against HDM2-positive cancers.
Keywords: Doxil; HDM2 overexpressed tumors; PEGylated liposome doxorubicin; PNC27 peptide; cancer treatment; targeting ligand.