Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA

Swati Koppu, Yew Jinn Oh, R. Edrada-Ebel, David R. Blatchford, L. Tetley, R. Tate, Christine Dufès

Research output: Contribution to journalArticle

  • 68 Citations

Abstract

The possibility of using genes as medicines to treat cancer is limited by the lack of safe and efficacious delivery systems able to deliver therapeutic genes selectively to tumors by intravenous administration. We investigate if the conjugation of the polypropylenimine dendrimer to transferrin, whose receptors are overexpressed on numerous cancers, could result in a selective gene delivery to tumors after intravenous administration, leading to an increased therapeutic efficacy. The objectives of this study are to evaluate the targeting and therapeutic efficacies of a novel transferrin-bearing polypropylenimine dendrimer. The intravenous administration of transferrin-bearing polypropylenimine polyplex resulted in gene expression mainly in the tumors. Consequently, the intravenous administration of the delivery system complexed to a therapeutic DNA led to a rapid and sustained tumor regression over one month, with long-term survival of 100% of the animals (90% complete response, 10% partial response). The treatment was well tolerated by the animals, with no apparent signs of toxicity. Transferrin-bearing polypropylenimine may thus be a promising gene delivery system for cancer therapy.
LanguageEnglish
Pages215-221
Number of pages7
JournalJournal of Controlled Release
Volume143
Issue number2
DOIs
StatePublished - 19 Apr 2010

Fingerprint

Gene Transfer Techniques
Plasmids
DNA
Intravenous Administration
Transferrin
Neoplasms
Dendrimers
Therapeutics
Genes
Transferrin Receptors
Gene Expression
poly(propyleneimine)

Keywords

  • cancer therapy
  • transferrin
  • tumor targeting
  • gene delivery
  • polypropylenimine dendrimer
  • polyethylenimine/dna complexes
  • agents
  • niosomes
  • vesicles

Cite this

@article{3bf9b345a0584bcb95d49eb095146bda,
title = "Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA",
abstract = "The possibility of using genes as medicines to treat cancer is limited by the lack of safe and efficacious delivery systems able to deliver therapeutic genes selectively to tumors by intravenous administration. We investigate if the conjugation of the polypropylenimine dendrimer to transferrin, whose receptors are overexpressed on numerous cancers, could result in a selective gene delivery to tumors after intravenous administration, leading to an increased therapeutic efficacy. The objectives of this study are to evaluate the targeting and therapeutic efficacies of a novel transferrin-bearing polypropylenimine dendrimer. The intravenous administration of transferrin-bearing polypropylenimine polyplex resulted in gene expression mainly in the tumors. Consequently, the intravenous administration of the delivery system complexed to a therapeutic DNA led to a rapid and sustained tumor regression over one month, with long-term survival of 100{\%} of the animals (90{\%} complete response, 10{\%} partial response). The treatment was well tolerated by the animals, with no apparent signs of toxicity. Transferrin-bearing polypropylenimine may thus be a promising gene delivery system for cancer therapy.",
keywords = "cancer therapy, transferrin, tumor targeting, gene delivery, polypropylenimine dendrimer, polyethylenimine/dna complexes, agents, niosomes, vesicles",
author = "Swati Koppu and Oh, {Yew Jinn} and R. Edrada-Ebel and Blatchford, {David R.} and L. Tetley and R. Tate and Christine Duf{\`e}s",
year = "2010",
month = "4",
day = "19",
doi = "10.1016/j.jconrel.2009.11.015",
language = "English",
volume = "143",
pages = "215--221",
journal = "Journal of Controlled Release",
issn = "0168-3659",
number = "2",

}

Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA. / Koppu, Swati; Oh, Yew Jinn; Edrada-Ebel, R.; Blatchford, David R.; Tetley, L.; Tate, R.; Dufès, Christine.

In: Journal of Controlled Release, Vol. 143, No. 2, 19.04.2010, p. 215-221.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA

AU - Koppu,Swati

AU - Oh,Yew Jinn

AU - Edrada-Ebel,R.

AU - Blatchford,David R.

AU - Tetley,L.

AU - Tate,R.

AU - Dufès,Christine

PY - 2010/4/19

Y1 - 2010/4/19

N2 - The possibility of using genes as medicines to treat cancer is limited by the lack of safe and efficacious delivery systems able to deliver therapeutic genes selectively to tumors by intravenous administration. We investigate if the conjugation of the polypropylenimine dendrimer to transferrin, whose receptors are overexpressed on numerous cancers, could result in a selective gene delivery to tumors after intravenous administration, leading to an increased therapeutic efficacy. The objectives of this study are to evaluate the targeting and therapeutic efficacies of a novel transferrin-bearing polypropylenimine dendrimer. The intravenous administration of transferrin-bearing polypropylenimine polyplex resulted in gene expression mainly in the tumors. Consequently, the intravenous administration of the delivery system complexed to a therapeutic DNA led to a rapid and sustained tumor regression over one month, with long-term survival of 100% of the animals (90% complete response, 10% partial response). The treatment was well tolerated by the animals, with no apparent signs of toxicity. Transferrin-bearing polypropylenimine may thus be a promising gene delivery system for cancer therapy.

AB - The possibility of using genes as medicines to treat cancer is limited by the lack of safe and efficacious delivery systems able to deliver therapeutic genes selectively to tumors by intravenous administration. We investigate if the conjugation of the polypropylenimine dendrimer to transferrin, whose receptors are overexpressed on numerous cancers, could result in a selective gene delivery to tumors after intravenous administration, leading to an increased therapeutic efficacy. The objectives of this study are to evaluate the targeting and therapeutic efficacies of a novel transferrin-bearing polypropylenimine dendrimer. The intravenous administration of transferrin-bearing polypropylenimine polyplex resulted in gene expression mainly in the tumors. Consequently, the intravenous administration of the delivery system complexed to a therapeutic DNA led to a rapid and sustained tumor regression over one month, with long-term survival of 100% of the animals (90% complete response, 10% partial response). The treatment was well tolerated by the animals, with no apparent signs of toxicity. Transferrin-bearing polypropylenimine may thus be a promising gene delivery system for cancer therapy.

KW - cancer therapy

KW - transferrin

KW - tumor targeting

KW - gene delivery

KW - polypropylenimine dendrimer

KW - polyethylenimine/dna complexes

KW - agents

KW - niosomes

KW - vesicles

U2 - 10.1016/j.jconrel.2009.11.015

DO - 10.1016/j.jconrel.2009.11.015

M3 - Article

VL - 143

SP - 215

EP - 221

JO - Journal of Controlled Release

T2 - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 2

ER -