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Bacterial-derived magnetosomes as nanocarriers for cancer-killing oncolytic viruses.


Department of Oncology and Metabolism

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Dr M Muthana , Dr F Howard Applications accepted all year round Self-Funded PhD Students Only

About the Project

Dysfunctional cellular processes that are the markers of neoplasms provide the ideal environment for viral infection including sustained proliferation and resistance to cell death. This makes cancers perfect targets for oncolytic viruses (OV). These cancer-killing viruses destroy cancer cells directly but also via activation of the immune system, initiating immune cell death. Unfortunately this also contributes to their rapid clearance when administered systemically. To circumnavigate the variable response rates seen in clinical trials against cancer [1] investigators are utilising drug delivery systems (liposomes, cell carriers, polymers) to improve bioavailability and reduce toxicity [2]. The combination of these nanocarriers together with OV’s has demonstrated improved efficacy but not overwhelmingly so. Once within the circulation, the majority of these drug delivery systems (DDSs) rely on passive transport to reach their target site. By utilising the magnetic properties of metallic nanoparticles called magnetosomes, which are extracted from MTB, we hope to guide magnetosomes attached to OV’s (MAG-OV) to tumour targets via the use of external magnets [3]. Different strains of MTB produce different shapes of magnetosomes and provide an opportunity to study the impact of this on their pharmacokinetics (PK), biodistribution, intratumoural penetration and tumour bioavailability [2, 3] whilst enabling other confounding physicochemical characteristics to remain unaltered.

There is a need for a less discriminatory DDS to mitigate the problems associated with tumour heterogeneity. Therefore, by focusing on the intrinsic properties of the carrier itself there is an opportunity to create a platform for the development of nanomedicines for multiple cancers. The purpose of this work is to investigate the effects of shape as well as administration route to increase the therapeutic window of MAG-OV, which will then complement an active guidance strategy to generate improved efficacy. Whilst this project focuses on OV this approach could be applied to other cancer treatments.

Funding Notes

This project is optn to self-funded students only.

Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research experience.

References

Enquiries:
Interested candidates should in the first instance contact Munitta Muthana, [email protected]

How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select Oncology and Metabolism as the department.


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