Systemic cancer therapies such as chemotherapy and emerging gene therapies are often limited by poor tumour selectivity, dose-limiting toxicity, and limited therapeutic response in solid tumours. Nanomedicine offers the potential to overcome these limitations by engineering delivery systems able to specifically target tumours, accumulate preferentially at the disease site, and release their therapeutic payload in response to tumour-specific signals.

Our research group has demonstrated the efficacy of targeted delivery systems, such as transferrin-bearing dendrimers and lactoferrin-conjugated nanoparticles, in achieving tumour regression and enhanced gene expression in vivo, with minimal off-target effects.

This project will build upon these successful platforms to design and evaluate advanced nanocarriers, including dendrimers, zein-based nanoparticles, and hybrid lipid-polymer structures, for the systemic delivery of anti-cancer agents, tailored to your interests.

Core objectives

• synthesis, and characterisation of tumour-targeted nanomedicines (e.g. dendrimers, lipid-polymer hybrids, hydrogels, zein hybrids)
• functionalisation with tumour-specific ligands to enable receptor-mediated uptake
• encapsulation and delivery of therapeutic payloads, including small-molecule anticancer drugs, genetic materials (i.e.  plasmid DNA, siRNA, CRISPR-Cas9 systems), immunomodulators or cytokines
• in vitro testing of cytotoxicity, cellular uptake, gene expression, and tumour-specific delivery
• In vivo studies to evaluate biodistribution, therapeutic efficacy, and safety

Adaptable themes

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

• tumour-targeted drug and gene nanomedicines
• dual delivery of drugs and genes for synergistic anticancer effects
• development of tumour-microenvironment-responsive nanomedicines (e.g., redox or pH-sensitive systems)
• delivery of CRISPR-Cas9 for genome editing in cancer cells
• biomaterial-based immunotherapies using nanocarrier platforms
• development of novel hydrogels for biomedical applications

Research significance

This multidisciplinary project offers strong translational potential for systemic cancer therapy. The use of receptor-targeted, biodegradable nanocarriers addresses a critical need for safe, effective cancer treatments. It combines pharmaceutical sciences, materials chemistry, and oncology to train researchers in cutting-edge therapeutic technologies.

Techniques you will learn

• synthesis and physicochemical characterisation of nanomedicines (size, zeta potential, drug/gene loading, release profile)
• surface ligand conjugation and PEGylation
• in vitro cell culture, cytotoxicity assays, transfection studies, confocal microscopy, flow cytometry
• in vivo biodistribution, tumour targeting, and therapeutic efficacy studies

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 

• 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 

• 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 

• 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 

• 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 

• 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

• 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 

• 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

• 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 

• 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

   

• J. Meewan, S. Somani, P. Laskar, C. Irving, M. Mullin, C.W. Roberts, S. Woods, V.A. Ferro, A.R. Alzahrani, R. Burchmore, S. Weidt, S. McGill, C. Dufès, Limited impact of the protein corona on the cellular uptake of PEGylated zein micelles by melanoma cancer cells, Pharmaceutics, 14 (2) (2022) 429

• J. Almowalad, P. Laskar, S. Somani, J. Meewan, R.J. Tate, C. Dufès, Lactoferrin- and dendrimer-bearing gold nanocages for stimulus-free DNA delivery to prostate cancer cells, International Journal of Nanomedicine, 17 (2022) 1409-1421 

• J. Meewan, S. Somani, J. Almowalad, P. Laskar, M. Mullin, G. MacKenzie, S. Khadke, Y. Perrie, C. Dufès, Preparation of zein-based nanoparticles: nanoprecipitation versus microfluidic-assisted manufacture, effects of PEGylation on nanoparticle characteristics and cellular uptake by melanoma cells, International Journal of Nanomedicine, 17 (2022) 2809-2822

• K. Maeyouf, I. Sakpakdeejaroen, S. Somani, J. Meewan, H. Ali-Jerman, P. Laskar, M. Mullin, G. MacKenzie, R. J. Tate, C. Dufès, Transferrin-bearing, zein-based hybrid lipid nanoparticles for drug and gene delivery to prostate cancer cells, Pharmaceutics, 15 (11) (2023) 2643 

• H. Ali-Jerman, Z. Al-Quraishi, A. Muglikar, Y. Perrie, R. J. Tate, M. Mullin, G. McNeill, G. Mackenzie, C. Dufès, Enhancing transfection in glioma cells: comparison of microfluidic versus manual polypropylenimine dendriplex formation, International Journal of Nanomedicine, 19 (2024) 12189-12203