Postgraduate research opportunities Development of novel tumour-targeted nanomedicines for cancer therapy

The possibility of using non-viral 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 characterisation of novel tumour-targeting delivery systems
• the evaluation of the tumour delivery and therapeutic efficacy of these systems in vitro and in vivo

Specifically, we currently have a very diversified portfolio of research projects, depending on the specific interests of the PhD candidate, including:

• development of non-viral CRISPR-Cas9 technologies
• tumour microenvironment-sensitive drug & gene delivery systems
• tumour-targeted drug & gene nanomedicines
• biomaterial-based immunotherapies
• development of novel hydrogels for biomedical applications
• brain-targeted drug & gene delivery systems

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

Further information

References

• 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) (IF 2009: 5.949)
• 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 (IF 2010: 7.883)
• 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 (IF 2013: 5.978)
• S. Somani, G. Robb, B. S. Pickard, C. Dufès, Enhanced gene expression in the brain following intravenous administration of lactoferrin-bearing polypropylenimine dendriplex, Journal of Controlled Release, 217 (2015) 235-242 (IF 2014: 7.705)
• 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 (IF 2016: 7.786)
• N. Altwaijry, S. Somani, J.A. Parkinson, R.J. Tate, P. Keating, M. Warzecha, G.R. Mackenzie, H.Y. Leung, C. Dufès, Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL and interleukin-12, Drug Delivery, 25(1) (2018) 679-689 (IF 2016: 6.402)
• P. Laskar, S. Somani, N. Altwaijry, M. Mullin, D. Bowering, M. Warzecha, H.Y. Leung, C. Dufès, Redox-sensitive, cholesterol-bearing PEGylated poly(propyleneimine)-based dendrimersomes for drug and gene delivery to cancer cells, Nanoscale, 10 (2018) 22830-22847 (IF 2017: 7.233)
• P. Laskar, S. Somani, S.J. Campbell, M. Mullin, P. Keating, R.J. Tate, C. Irving, H.Y. Leung, C. Dufès, Camptothecin-based dendrimersomes for gene delivery and redox-responsive drug delivery to cancer cells, Nanoscale, 11(42) (2019) 20058-20071 (IF 2018: 6.970)
• I. Sakpakdeejaroen, S. Somani, P. Laskar, C. Irving, M. Mullin, C. Dufès, Anti-tumor activity of intravenously administered plumbagin entrapped in targeted nanoparticles (Journal of Biomedical Nanotechnology, 16(1) (2020) 85-100 (IF 2018: 5.068)
• P. Laskar, S. Somani, M. Mullin, R. J. Tate, M. Warzecha, D. Bowering, P. Keating, C. Irving, H. Y. Leung, C. Dufès*, Octadecyl chain-bearing PEGylated poly(propyleneimine)-based dendrimersomes: physicochemical studies, redox-responsiveness, DNA condensation, cytotoxicity and gene delivery to cancer cells, Biomaterials Science, 9(4) (2021) 1431-1448 (IF 2020: 6.183)
• I. Sakpakdeejaroen, S. Somani, P. Laskar, M. Mullin, C. Dufès *, Regression of melanoma following intravenous injection of plumbagin entrapped in transferrin-conjugated, lipid–polymer hybrid nanoparticles, International Journal of Nanomedicine, 16 (2021) 2615-2631 (IF 2020: 5.115)
• J. Almowalad, S. Somani, P. Laskar, J. Meewan, R.J. Tate, M. Mullin, C. Dufès*, Lactoferrin-bearing gold nanocages for gene delivery in prostate cancer cells in vitro, International Journal of Nanomedicine, 16 (2021) 4391-4407 (IF 2021: 6.4)