PhD Study : Alternative therapeutic options for ocular melanoma (OM) using nanoparticles for enhanced delivery

Summary

There were 750 new cases of eye cancer in the UK in 2014, that’s around 2 cases diagnosed every day. It is now widely accepted that melanoma is better treated by a multifaceted combination therapy strategy. Aside from surgery, radiotherapies are currently available for ocular melanoma; particle beam, transpupillary thermotherapy, laser photocoagulation, gamma knife stereotactic radiosurgery and local surgical resection. More recently Photodynamic Therapy (PDT) is emerging as a promising alternative. As the mechanism of action for PDT is very different to each of these three therapies, the potential for enhanced efficacy with any of these combinations is available. Photodynamic Therapy (PDT) is a treatment modality involving three components; a photosensitiser (PS), light and molecular oxygen. These agents are non-toxic alone, but when combined trigger reactive-oxygen species (ROS) generation resulting in oxidative stress and cytotoxicity. PDT is beneficial in reducing the occurrence of tumour resistance as multiple forms of ROS are produced simultaneously. The main problem with PDT is getting the light to the appropriate depth of penetration, with melanoma in particular difficult to penetrate.

This research proposes a novel formulation of a combination therapy for ocular melanoma to include a photosensitising (PS) agent alongside a targeting antimicrobial peptide (AMP) encapsulated within a nanoparticle for enhanced delivery.  The applicants have previously shown Rose Bengal (RB) to be an efficient PS for use in PDT, an efficacy that can be further enhanced by specific cell targeting. As a result of cellular heterogeneity in tumours, AMPs have emerged as a novel means of enabling transmembrane delivery of active agents.  We intend to exploit them in order to provide targeted delivery of the AMP conjugated to RB.  Because of tumour immune suppression, we will also exploit novel immunotherapeutics in combination with our PDT-based approach. Finally, with the use of nanotechnologies, this research will investigate the ability to deliver this enhanced treatment therapy as a topical suspension for ocular delivery. If successful we would be broadening the treatment options for patients with melanoma by providing both targeted neoadjuvant and adjuvant options.

Overall Aim: Develop the potential of PDT and other targeted synergistic therapies for the adjuvant and neoadjuvant treatment of ocular melanoma (OM) using nano/micro particles for enhanced delivery. Specific Aim 1: Establish the efficacy of RB-(KLAKLAK)2 conjugate and daylight PDT in OM cells. Specific aim 2: Investigate the potential of synergistic effect by combining PDT with chemo- and immunotherapies for concomitant delivery. Specific Aim 3: Formulation of therapies into a suitable drug delivery system and subsequent cellular uptake studies. Specific Aim 4: Utilising an ex-vivo ocular model to establish the effectiveness of the drug delivery system.

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
• A comprehensive and articulate personal statement

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%
• Completion of Masters at a level equivalent to commendation or distinction at Ulster
• Research project completion within taught Masters degree or MRES
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications - peer-reviewed
• Experience of presentation of research findings

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