Therapeutic efficacy of intravenously administered transferrin-conjugated dendriplexes on prostate carcinomas

Abstract

Aim: Improved treatments for prostate cancer are critically needed in order to overcome metastasis and lethal recurrence. Intravenously administered gene therapy would be an attractive anticancer treatment strategy; however, the lack of suitable carrier systems able to selectively deliver therapeutic genes to tumors has so far limited this investigation. Given that transferrin receptors are overexpressed on prostate cancer cells, the purpose of this study is to determine whether transferrin-conjugated dendriplexes encoding TNF-α, TNF-related apoptosis-inducing ligand and IL-12 would suppress the growth of prostate cancer cell lines in vitro and in vivo. Materials & methods: Transferrin-conjugated dendriplexes encoding TNF-α, TNF-related apoptosis-inducing ligand and IL-12 were intravenously administered to mice bearing subcutaneous PC-3 and DU145 tumors. Results: The administration of the transferrin-conjugated generation 3 diaminobutyric polypropylenimine dendriplex encoding TNF-α resulted in tumor suppression for 60% of PC-3 and 50% of DU145 prostate tumors. Conclusion: These dendriplexes hold great potential as a novel approach for prostate cancer therapy.