Abstract

Tumour Regression after Intravenous Administration of Novel Tumour-targeted Nanomedicines

Christine Dufes, Senior Lecturer, University of Strathclyde

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 tumours by intravenous administration, without secondary effects to healthy tissues. In order to remediate to this problem, we investigated if the conjugation of the polypropylenimine dendrimer to transferrin, whose receptors are overexpressed on numerous cancers, could result in a selective gene delivery to tumours 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 tumours. Consequently, the intravenous administration of the delivery system complexed to a therapeutic DNA encoding TNF led to a rapid and sustained tumour regression over one month (90% complete response, 10% partial response on A431 human epidermoid tumours). It also resulted in tumour suppression for 60% of PC-3 and 50% of DU145 prostate tumours. The treatment was well tolerated by the animals, with no apparent signs of toxicity. Transferrin-bearing polypropylenimine is therefore a highly promising delivery system for cancer therapy.