Christine Dufès
University of Strathclyde, UK
Title: Tumour regression after intravenous administration of novel tumour-targeted nanomedicines
Biography
Biography: Christine Dufès
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 tumours by intravenous administration, without secondary effects to healthy tissues. In order to remediate to this problem, we investigated if the conjugation of the generation 3 diaminobutyric polypropylenimine dendrimer to transferrin and lactoferrin, 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 intravenous administration of transferrin-bearing and lactoferrin-bearing polypropylenimine dendriplexes resulted in gene expression mainly in the tumours. Consequently, the intravenous administration of the transferrin-bearing delivery system complexed to a therapeutic DNA encoding tumour necrosis factor (TNF)α led to 90% tumour suppression over one month on A431 epidermoid tumours. It also resulted in tumour suppression for 60% of PC-3 and 50% of DU145 prostate tumours. Furthermore, the intravenous administration of the lactoferrin-bearing targeted dendriplexes encoding TNFα led to the complete suppression of 60% of A431 tumours and up to 50% of B16-F10 skin tumours over one month. Transferrin- and lactoferrin-bearing polypropylenimine dendrimers are therefore highly promising delivery systems for cancer therapy.