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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6 Citations (Scopus)

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.
LanguageEnglish
Pages679-689
Number of pages11
JournalDrug Delivery
Volume25
Issue number1
Early online date1 Mar 2018
DOIs
Publication statusE-pub ahead of print - 1 Mar 2018

Fingerprint

Lactoferrin
Interleukin-12
Intravenous Administration
Prostate
Tumor Necrosis Factor-alpha
Prostatic Neoplasms
Neoplasms
Dendrimers
Therapeutics
Gene Transfer Techniques
poly(propyleneimine)
Genetic Therapy
Transfection
Genes

Keywords

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

Cite this

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title = "Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL and interleukin-12",
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.",
keywords = "prostrate cancer, gene therapy, dendrimer, lactoferrin, nanoparticles, atomic force microscopy",
author = "Najla Altwaijry and Sukrut Somani and Parkinson, {John A.} and Tate, {Rothwelle J.} and Patricia Keating and Monika Warzecha and MacKenzie, {Graeme R.} and Leung, {Hing Y.} and Christine Duf{\`e}s",
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T1 - Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL and interleukin-12

AU - Altwaijry, Najla

AU - Somani, Sukrut

AU - Parkinson, John A.

AU - Tate, Rothwelle J.

AU - Keating, Patricia

AU - Warzecha, Monika

AU - MacKenzie, Graeme R.

AU - Leung, Hing Y.

AU - Dufès, Christine

PY - 2018/3/1

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N2 - 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.

AB - 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.

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KW - dendrimer

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KW - nanoparticles

KW - atomic force microscopy

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