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

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 (Lf) receptors are overexpressed on prostate cancer cells, we hy...

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Bibliographic Details
Published in:Drug delivery 2018-11, Vol.25 (1), p.679-689
Main Authors: Altwaijry, Najla, Somani, Sukrut, Parkinson, John A., Tate, Rothwelle J., Keating, Patricia, Warzecha, Monika, Mackenzie, Graeme R., Leung, Hing Y., Dufès, Christine
Format: Article
Language:English
Subjects:
Administration, Intravenous
Animals
Cell Line, Tumor
dendrimer
Gene therapy
Genetic Therapy - methods
Humans
Interleukin-12 - administration & dosage
Interleukin-12 - genetics
lactoferrin
Lactoferrin - administration & dosage
Male
Mice
Mice, Inbred BALB C
nanoparticles
Polypropylenes - administration & dosage
Prostate cancer
Prostatic Neoplasms - genetics
Prostatic Neoplasms - therapy
TNF-Related Apoptosis-Inducing Ligand - administration & dosage
TNF-Related Apoptosis-Inducing Ligand - genetics
Tumor Necrosis Factor-alpha - administration & dosage
Tumor Necrosis Factor-alpha - genetics
Tumors
Xenograft Model Antitumor Assays - methods
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Summary: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 (Lf) receptors are overexpressed on prostate cancer cells, we hypothesized that the conjugation of Lf 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 Lf-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. Lf-bearing generation 3-polypropylenimine dendrimer is therefore a highly promising delivery system for non-viral gene therapy of prostate cancer.
ISSN:1071-7544
1521-0464
DOI:10.1080/10717544.2018.1440666