Cancer therapy; tumour targeting; delivery system; gene therapy, nanomedicine

The possibility of using non-viral gene delivery systems for the treatment of cancer is currently limited by their failure to specifically reach tumours after intravenous administration, without secondary effects on normal tissues. We have recently demonstrated that the intravenous administration of therapeutic DNA complexed to polypropylenimine dendrimer bearing transferrin, whose receptors are overexpressed on most cancers, led to a rapid and sustained tumour regression over one month, with complete disappearance of 90% of the tested tumours and regression of the remaining ones for the cancer model tested. These results are highly important, as there is currently no gene medicine commercially available for the intravenous treatment of cancer.

Building on the promising results already obtained, the proposed project aims to develop novel tumour-targeted nanomedicines and to evaluate their targeting and therapeutic efficacy on cancers. Specifically, the key objectives are:

        - the preparation and characterization of novel tumour-targeting delivery systems

        - the evaluation of the tumour delivery and therapeutic efficacy of these systems in vitro and in vivo.

The student will have the opportunity to learn a wide range of multidisciplinary techniques:  synthesis and characterization of the nanomedicines, cell culture, in vitro analysis techniques (cytotoxicity assay, confocal microscopy) and in vivo analysis.

- S. Koppu, Y.J. Oh, R. Edrada-Ebel, D.R. Blatchford, L. Tetley, R. J. Tate, C. Dufès, Tumor regression after systemic administration of a novel tumor-targeted gene delivery system carrying a therapeutic plasmid DNA, Journal of Controlled Release, 143 (2010) 215-221 (with cover and editorial)

- H. Aldawsari, R. Edrada-Ebel, D.R. Blatchford, R. J. Tate, L. Tetley, C. Dufès, Enhanced gene expression in tumors after intravenous administration of arginine-, lysine- and leucine-bearing polypropylenimine polyplex, Biomaterials, 32 (2011) 5889-5899

- M. Al Robaian, K.Y. Chiam, D.R. Blatchford, C. Dufès, Therapeutic efficacy of intravenously administered transferrin-conjugated dendriplexes encoding TNF-α, TRAIL and interleukin-12 on prostate carcinomas, Nanomedicine, 9(4) (2014) 421-434

- L. Y. Lim, P.Y. Koh, S. Somani, M. Al Robaian, R. Karim, Y.L. Yean, J. Mitchell, R.J. Tate, R. Edrada-Ebel, D.R. Blatchford, M. Mullin, C. Dufès, Tumor regression following intravenous administration of lactoferrin- and lactoferricin-bearing dendriplexes, Nanomedicine : Nanotechnology, Biology and Medicine, 11 (2015) 1445-1454