PhD Studentship: Biorelevant Metal Complexes as Potential Hypoxic Activated Prodrugs for the Treatment of Cancer

Supervisor: Dr Rianne M. Lord

Funding Availability: 3.5 years of home fees and stipend funded by the University of Warwick and open only to Home students.

*Please note - ELIGIBILITY - Applicants from overseas ARE eligible for this post, but need to find financial means to bridge the gap between home and overseas study fees.

Deadline: The project will remain open until a suitable candidate is identified. Early application is encouraged.

Project Description: Platinum-based metallodrugs dominate the clinic for the treatment of cancer and have done so for >40 years; however, they have some major drawbacks associated with their use. These include severe patient side effects due to the lack of cancer cell selectivity and increased cancer cell resistance. Such drawbacks have led researchers to design and test new transition metal complexes as potential alternatives to platinum. Ideally, these new designs should focus on different intracellular modes of action and/or creation of non-toxic prodrugs which can be activated to a toxic form in the cancer environments.

This research project will focus on the design of biorelevant metallodrugs, which are relatively abundant, cheaper, and less toxic than platinum, and where the metal centre can perform one electron oxidation/reductions in cellular environments. All new complexes will undergo in-depth cellular studies to ensure they are non-toxic and have suitable redox potentials, and we will provide understanding of the drug’s potential to target hypoxic (low oxygen) cancer environments, creating new hypoxic activated prodrugs (HAPs).

The Lord Group recently embarked on a novel project focused on understand the modes of action of vanadium metal complexes, in particular, their various intracellular oxidation states to fine-tune their cellular activities. Whilst these complexes have been more effective and selective in comparison to platinum, their HAPs potential has been inhibited by low stability and solubility. Herein, we will design new vanadium complexes with varying oxidation states, incorporate them into polymer systems to overcome the issues of stability and solubility, and provide a deeper understanding their HAPs potential.

The successful candidate will be supervised by the Lord Group in the Department of Chemistry and receive extensive training in synthesis and analysis of small molecules, polymers, and all necessary cell culture techniques for determination of cellular modes of action. These skills will be supported by access to University of Warwick’s excellent technical team and Research Technology Platforms and our collaborations with the School of Life Sciences and Warwick Medical School. The candidate will also benefit from comprehensive training in technical scientific skills, transferable skills, and career development, and they will be supported to attend national and international conferences to present their work and develop their networks. The project will be part of an exciting interdisciplinary collaboration, and benefit from the inclusive research environment in the Department of Chemistry and the University as a whole.

Requirements: Applicants should have a good degree (at least 2.1 or equivalent) in chemistry, or other relevant discipline. No prior experience in biology is require, but the applicants should have a strong research interest in drug discovery and chemical biology.

How to apply: Interested candidates should contact Dr Lord by email (Rianne.lord@warwick.ac.uk) in the first instance with a copy of their CV and a covering letter outlining their research interests and why they are interested in the position. Details on the formal application procedure can be found at http://www.go.warwick.ac.uk/pgapply,

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