Transferrin-conjugated liposome/IL-12 pDNA complexes for cancer gene therapy in mice

Abstract

Transferrin (T-f) has been used as a targeting ligand for delivering liposome/interleukin-12 (IL-12) pDNA complexes to cancer cells mostly due to the greater number of transferrin receptors (TfR) found on tumor cells than on normal cells. Tf was conjugated to liposomes via the reaction of MPB-PE with thiol groups of Tf introduced by a heterobifunctional cross-linking agent, N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP). Four days after C-26 inoculation when the tumor volume reached similar to 100 mm(3), tumor-bearing Balb/c mice were injected intravenously with T-f-liposome/IL-12 pDNA complexes twice a week for 3 weeks. Significant suppression of tumor growth was achieved in the group treated with the T-f-liposome/IL-12 pDNA complexes, with a dose of 10 mu g of IL-12 pDNA showing the highest suppression effect among the tested doses. Similar results were obtained when the therapy was initiated one day after tumor inoculation, although in this case 30 mu g IL-12 pDNA/T-f-liposome complexes showed a significant suppression of tumor growth between 19 and 23 days after tumor inoculation. This result indicates that the transferrin receptor-targeted liposomal system is an efficient delivery agent of therapeutic genes, such as IL-12, in mice and that its potential clinical use warrants further research investigation.