In the protein-targeted therapy for cancer, transferrin (Tf) is used to reach a selective and specific target in cancer cells. Tf is used conjugated to chemotherapeutic drugs, insulin, toxins, antibodies, polymers, nanoparticles, lipoplexes and liposomes. Using this latter approach, hydrophobically derivatized Tf was incorporated to liposomal bilayers. The biological activity of Tf-liposome was tested using MXT-B2 cells, a metastatic mammary carcinoma cell line. In Tf binding assays, the Scatchard analysis indicated 4.5 x 10(5) Tf receptors/cell. In cell growth assays, Tf-liposomes stimulated cell growth in a dose-dependent manner, up to a maximum of 32% of the total free Tf stimulation. Following this, we prepared Tf-liposomes encapsulating adriamycin (ADR) at two different ADR-to-lipid ratios. In vitro cytotoxicity assays against MXT-B2 cells gave IC50 values 2.1-times lower for Tf-liposomal ADR in comparison to control liposomal ADR. However, similar IC50 values were found for low ADR-to-lipid ratio Tf-liposomal ADR, as well as for control liposomal ADR. The free Tf added in excess increased the IC50, value of Tf-liposomal ADR by 51%, while the IC50 value of control liposomal ADR was unaffected, supporting a receptor-mediated mechanism of targeting by Tf. In addition, the lower IC50 value is correlated with a higher total of ADR accumulation in the cells.
