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...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.展开更多
基金National Natural Science Foundation of China(Grant No.81130059)the National Research Fund for Fundamental Key Project(Grant No.2009CB930300)
文摘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.
