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

Koppu, Swati and Oh, Yew Jinn and Edrada-Ebel, R. and Blatchford, David R. and Tetley, L. and Tate, R. and Dufès, Christine (2010) Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA. Journal of Controlled Release, 143 (2). pp. 215-221. ISSN 0168-3659

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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.