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

The therapeutic potential of natural products with promising anti-cancer properties (nutraceuticals), such as the vitamin E extract tocotrienol and the green tea extract epigallocatechin gallate (EGCG), is limited by the failure of these drugs to specifically reach tumours after intravenous administration, without secondary effects on normal tissues. We have recently demonstrated that the intravenous administration of novel tumour-targeted vesicles entrapping either tocotrienol or EGCG led to tumour regression, with the complete disappearance of 40% of the tested melanoma tumours, contrarily to that observed with controls. It was the first time that intravenously administered formulations of tocotrienol and EGCG were shown to result to complete tumour suppression. These results were highly promising, but still require to be optimized.

Building on the promising results already obtained, the proposed project aims to develop novel tumour-targeted nanomedicines entrapping other promising nutraceuticals, 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:  preparation and characterization of the nanomedicines, cell culture, in vitro analysis techniques (cytotoxicity assay, confocal microscopy) and in vivo analysis.

- J.Y. Fu, D.R. Blatchford, L. Tetley, C. Dufès, Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles, Journal of Controlled Release, 140 (2009) 95-99

- J.Y. Fu, W. Zhang, D.R. Blatchford, L. Tetley, G. McConnell, C. Dufès, Novel tocotrienol-entrapping vesicles can eradicate solid tumors after intravenous administration, Journal of Controlled Release, 154 (2011) 20-26) (mentioned in the editorial)

- F. Lemarié, C.W. Chang, D.R. Blatchford, R. Amor, G. Norris, L. Tetley, G. McConnell, C. Dufès, Anti-tumor activity of the tea polyphenol epigallocatechin gallate encapsulated in targeted vesicles after intravenous administration, Nanomedicine, 8(2) (2013) 181-192

- J.Y. Fu and C. Dufès, Anti-cancer efficacy of intravenously administered tumor-targeted vesicles entrapping tocotrienol, Pharmaceutical Nanotechnology, 2 (4) (2014) 172-181

- R. Karim, S. Somani, M. Al Robaian, M. Mullin, R. Amor, G. McConnell, C. Dufès, Tumor regression after intravenous administration of targeted vesicles entrapping the vitamin E α-tocotrienol, Journal of Controlled Release, 246 (2017) 79-87