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

Altwaijry, N., Somani, S., Parkinson, J. A., Tate, R. J., Keating, P., Warzecha, M., Mackenzie, G. R., Leung, H. Y. and Dufès, C. (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. (doi: 10.1080/10717544.2018.1440666) (PMID:29493296) (PMCID:PMC6058574)

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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 (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.

Item Type:Articles
Additional Information:This work was financially supported by a grant from Worldwide Cancer Research [grant number 16-1303] to C.D. and H.Y.L. N.A. is in receipt of a PhD studentship from the Saudi Cultural Bureau and Princess Nourah 688 N. ALTWAIJRY ET AL. bint Abdulrahman University (Kingdom of Saudi Arabia) [grant number 15678]. S.S. is funded by a research grant from The Dunhill Medical Trust [grant number R463/0216]. This work was also supported by the Association for International Cancer Research.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leung, Professor Hing
Authors: Altwaijry, N., Somani, S., Parkinson, J. A., Tate, R. J., Keating, P., Warzecha, M., Mackenzie, G. R., Leung, H. Y., and Dufès, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Drug Delivery
Publisher:Taylor & Francis
ISSN:1071-7544
ISSN (Online):1521-0464
Published Online:01 March 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Drug Delivery 25(1):679-689
Publisher Policy:Reproduced under a Creative Commons License

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