Cancer is a challenging disease target, requiring wide-ranging strategies for intervention. Given the difficulties in treating recalcitrant tumours, multi-mode therapies are of significant potential value. Being able to attack a tumour with two different therapeutic approaches increases the chances of complete destruction, and hence full elimination of the disease.
In this project, we will aim to develop dual-mode therapeutic systems, which can potentially attack solid tumours in two different ways. Specifically, we will self-assemble nanosystems, which are then capable of being loaded with anti-tumour payloads both on their surfaces and within their interiors. Therapeutic agents will be bound to the surfaces of these nanosystems as a result of multivalent binding interactions, whilst those inside the nanosystems will be incorporated as a result of the hydrophobic effect.
Early stages of the project will focus on the synthesis of optimised drug delivery vehicles, and a full characterisation of their structure and properties. Specifically, their ability to interact with the two different therapeutic payloads will be fully characterised. This will require the application of quantitative physical organic and supramolecular assay methods to the nanomaterials synthesised. In later stages, we would also incorporate tumour-targeting units into the drug delivery vehicles.
The delivery vehicles will then be tested for their ability to destroy solid tumours in collaboration with researchers in Italy (led by Prof Sabrina Pricl, University of Trieste). The student will have the possibility to spend time working in the labs of collaborators to perform these studies.
In particular, we will aim to demonstrate that using two payloads within a single delivery vehicle increases the efficacy of the anti-tumour therapeutic, as in principle, a cancer cell exposed to the delivery vehicle will be exposed to both of the drugs, each of which will aim to destroy the cell via a different mechanism.
All research students follow our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills. All research students take the core training package which provides both a grounding in the skills required for their research, and transferable skills to enhance employability opportunities following graduation. Core training is progressive and takes place at appropriate points throughout a student’s higher degree programme, with the majority of training taking place in Year 1. In conjunction with the Core training, students, in consultation with their supervisor(s), select training related to the area of their research.
In the project, the student will gain excellent interdisciplinary training in a wide range of techniques from chemistry and pharmaceutical science, including organic synthesis, molecular characterisation, self-assembled nanomaterials (including characterisation techniques including light scattering and electron microscopy), gene binding studies, and drug formulation and release studies.
The student will be exceptionally well-trained for roles in industry. The biotechnology sector increasingly requires people with synthetic and analytical skills in nanomedicine. There are, therefore, many potential employability options for the student, in addition to post-doctoral opportunities in this highly-active research area.
The student will receive training as part of the Smith group, which has fortnightly progress/literature meetings. This group is part of the newly reinvigorated wider Molecular Materials Group, and from October 2018, joint group meetings will be held. The student will also be a member of COST Network CA17140 and will participate in network meetings on Cancer Nanomedicine – gaining a broad understanding of the challenges and potential solutions from across the chemistry/biology/physics/medicine interface. Facilitated by the COST network there will be opportunity for the student to spend time in a partner lab. COST network researchers will also visit the lab in York, and the PhD student will play an active role in hosting them.
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