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

Najla Altwaijry, Sukrut Somani, John A. Parkinson, Rothwelle J. Tate, Patricia Keating, Monika Warzecha, Graeme R. MacKenzie, Hing Y. Leung, Christine Dufès

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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.
Original languageEnglish
Pages (from-to)679-689
Number of pages11
JournalDrug Delivery
Volume25
Issue number1
Early online date1 Mar 2018
DOIs
Publication statusE-pub ahead of print - 1 Mar 2018

Keywords

  • prostrate cancer
  • gene therapy
  • dendrimer
  • lactoferrin
  • nanoparticles
  • atomic force microscopy

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