Gold nanoparticles (AuNP) with diameters of ~15nm can be readily synthesised in the laboratory and are the subject of a concerted international research effort, focused on developing new cancer therapies, with the aim of obtaining lower dosages and smaller side effects. For such a nanoparticle-delivery system to function effectively it must be capped with ligands to prevent capture by the immune system and to target and enter tumour cells. Generally these functions cannot be delivered by a single ligand and, hence, the development of these systems requires dual functionalization, attachments of typically a poly-ethylene glycol (PEG) ligand, to escape the immune system and also a peptide ligand to facilitate cell entry. At present the methods to prepare and analyse these ligand-functionalised particles are not fully developed, most notably, the arrangement and size of the ligands on the AuNP is still unknown.
This project tackles this issue for gold nanoparticles (AuNP) functionalised with PEG and peptide ligands, which represents a candidate system for the development of prostate cancer drugs. It will use principally atomic force microscopy (AFM) in a liquid environment. The supervisory team has well-established research expertise in AFM and SEM microscopy (P Lemoine), functionalisation of AuNP (D. Dixon) and cell biology (G Burke). It follows from an existing collaboration between Lemoine and Dixon, which has already yielded preliminary results on the AFM analysis of AuNP and an ongoing re-submission of an EPSRC proposal.
The rationale for this study is that, alternative solution analysis techniques used to date (FTIR, DLS, Zeta-potential) only give indirect information on size and arrangement.
The objectives of this project are;
1.To determine size and arrangement of competing PEG and peptide ligands on gold thin film surfaces using AFM microscopy and low kV field emission SEM microscopy. We will also study how blood proteins adhere to these surfaces to investigate their likely biological response.
2.To investigate these ligands on colloidal AuNP solutions, using, amongst others, the aforementioned solution analysis techniques.
3.To prepare and characterise ligand-functionalised AFM probes.
4.To use force spectroscopy and lateral force microscopy to analyse the interactions of these AFM probes with self-assembled AuNP layers and surface-immobilised cancer cells.
The overall delivery of the project is a better understanding of the arrangement and size of competing PEG and peptide ligands on AuNP as well as their interactions with cancer cells. This knowledge will result in more efficient functionalisation recipes, which will be tested in D. Dixon’s group, by well-established biological protocols as well as high-impact publications and RC funding bids. The proposed research is also aligned on the ‘healthy communities’ theme identified in the ‘five and fifty’ UU strategic plan, as well as its declared strategic priority to focus on research with impact.
Vice Chancellors Research Scholarships (VCRS)
The scholarships will cover tuition fees and a maintenance award of £14,777 per annum for three years (subject to satisfactory academic performance). Applications are invited from UK, European Union and overseas students.
The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 14,777 per annum for three years. EU applicants will only be eligible for the fees component of the studentship (no maintenance award is provided). For Non EU nationals the candidate must be "settled" in the UK.
Monday 19 February 2018
Mid March 2018
When applying for this PhD opportunity please quote reference number: