Abstract:

Tumor metastasis emerges as a crucial target for tumor therapy. In this study, a tumor metastasis targeting peptide (TMT) was conjugated to a lipid material (PEG-DSPE) to obtain the targeting compound (TMT-PEG-DSPE), which was used to construct the targeted liposomal doxorubicin (TMT-LS-DOX). We showed that TMT-LS-DOX presented satisfactory pharmaceutical characteristics. This metastasis-specific delivery system was tested in two highly metastatic breast cancer cell lines (MDA-MB-435S and MDA-MB-231) with a non-metastatic breast cancer cell line (MCF-7) as the control. The free TMT peptide itself showed no cytotoxicity even at the concentration of 100 μg/mL. Importantly, the enhanced cellular uptake of TMT-LS-DOX to both MDA-MB-435S and MDA-MB-231 cell lines was demonstrated as compared to MCF-7 cells, via a TMT-mediated mechanism demonstrated by a receptor competition study. In conclusion, the TMT modified nanocarriers might provide a strategy to enhance the specificity of chemotherapeutic agents to highly metastatic breast cancer.

Key words: Highly metastatic breast cancer, Tumor metastasis targeting peptide, Liposomes, Doxorubicin