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Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL and interleukin-12

Altwaijry, Najla and Somani, Sukrut and Parkinson, John A. and Tate, Rothwelle J. and Keating, Patricia and Warzecha, Monika and MacKenzie, Graeme R. and Leung, Hing Y. and Dufès, Christine (2018) Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL and interleukin-12. Drug Delivery, 25 (1). pp. 679-689. ISSN 1521-0464

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Abstract

The possibility of using gene therapy for the treatment of prostate cancer is limited by the lack of intravenously administered delivery systems able to safely and selectively deliver therapeutic genes to tumors. Given that lactoferrin receptors are overexpressed on prostate cancer cells, we hypothesized that the conjugation of lactoferrin to generation 3-diaminobutyric polypropylenimine dendrimer would improve its transfection and therapeutic efficacy in prostate cancer cells. In this study, we demonstrated that the intravenous administration of lactoferrin-bearing DAB dendriplexes encoding TNFα resulted in the complete suppression of 70% of PC-3 and 50% of DU145 tumors over one month. Treatment with DAB-Lf dendriplex encoding TRAIL led to tumor suppression of 40% of PC-3 tumors and 20% of DU145 tumors. The treatment was well tolerated by the animals. Lactoferrin-bearing generation 3-polypropylenimine dendrimer is therefore a highly promising delivery system for the gene therapeutic treatment of prostate cancer.