PhD Study : Gold Nanoparticles for Targeted Prostate Cancer Treatment

Summary

Nanosized gold particles (AuNPs) with diameters of 10-20nm have demonstrated great potential in the detection, imaging  and treatment of a range of cancers. Once inside a tumour, AuNPs can either be used for the targeted delivery of therapeutics, can be heated via a laser to destroy tumours or can be used to enhance the effectiveness of conventional radiotherapy, by increasing x-ray absorption. For example, it has been reported that mice containing mammary carcinomas injected with gold nanoparticles and subjected to conventional radiotherapy had a survival rate of 86% over 365 days compared to 20% for those receiving only radiotherapy  and 0% for the control group. Worldwide several AuNPs based treatment are currently undergoing clinical trials, although none are yet in routine use. In order to inhibit aggregation, to evade detection and removal by the immune system, and to target and enter tumour cells, it is necessary to functionalise the surface of the nanoparticles [1]. Typically, an antifouling polymer such as Polyethylene Glycol (PEG) is used together with ligands such as peptides, antibodies and therapeutics (e.g. chemotherapy drugs) to target and destroy tumours [2]. The arrangement of the ligands on the nanoparticle surface will directly influence their ability to interact with cells and thus the effectiveness of the AuNP treatment.

This project will focus on using advanced liquid stage atomic force microscopy (AFM) and the associated modelling, combined with high resolution mass spectroscopy (through collaborators in Leiden, Netherlands), transmission electron microscopy, light scattering and spectroscopy to investigate how the ligands are arranged on the nanoparticle surface. We will then go on determine the influence of this ligand arrangement on nanoparticles biological performance in terms of in vivo stability and cell response. In conjunction with our collaborators we have developed AuNPs systems capped with multiple peptides to drive cell uptake and target AuNPs to the cell nucleus. We have also synthesised and studied AuNPs capped with various custom peptides including a peptide which targets PSMA (Prostate Specific Membrane Antigen), which is overexpressed in prostate cancers. Preliminary cell work of PSMA targeting AuNPs synthesised in our lab has shown that they preferentially target cancer cells.

The project builds upon ongoing research, which has in recent years included two in-vivo experiments of novel AuNP systems, completed in conjunction with our collaborators at Queen Belfast [3]. Drs Dixon and Lemoine have been working together on functionalised AuNP for several years and Dr Farokh Payam brings specialised expertise in AFM modelling to the project, together with access to the specialist liquid AFM facilities available at his Spanish collaborators.

[1] Nicol J, Dixon D, Coulter JA.  Nanomedicine 10.8 (2015): 1315-1326.

[2] Harrison, E., Nicol, J., Macias–Montero, M., Burke, G. A., Coulter, J. A., Meenan, B. J., & Dixon, D. (2016). Materials Science and Engineering: C, 62, 710-718.

[3] Nicol, J. R., Harrison, E., O'Neill, S. M., Dixon, D., McCarthy, H. O., & Coulter, J. A. (2018). Nanomedicine: Nanotechnology, Biology and Medicine, 14(2), 439-449.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Masters at 65%
• Work experience relevant to the proposed project
• Publications - peer-reviewed

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living