PhD Project: Biological Evaluation of Ruthenium (II) complexes Targeted against Breast Cancers (BRUT BC)

Job Description

MCF-7 cells are primary tumour invasive breast ductal carcinoma which have both oestrogen and progesterone receptors. Tumour necrosis factor alpha (TNF alpha) inhibits the growth of MCF-7 breast cancer cells. Treatment with anti-oestrogens (i.e. Tamoxifen) can modulate the secretion of insulin-like growth factor binding proteins. The MCF-7 cell line is a widely used model for hormone-dependent human breast cancer. Ruthenium complexes previously prepared in TU Dublin 1, 2, 3, 4 will be investigated against the breast cancer cell lines including pre-treatment of the complex with photo-activation of atmospheric cold plasma (ACP). Breast cancer is on the increase and the triple negative breast cancer in particular is difficult to treat and target. MDA-MB-231 is a triple negative breast cancer cell line providing a model for human breast cancer which is unresponsive to oestrogen and does not overexpress oestrogen receptors. The MDA-MB-231 cell lines are highly invasive and metastatic human breast cancer cells which display the invasiveness by mediating the proteolytic degradation of the extracellular matrix (ECM), including basement membrane and several mechanical barriers to the ECM, through the increased expression of matrix metalloproteinases. Targeted therapies such as Herceptin and Tamoxifen have been transformational to HER2+ and oestrogen positive breast cancer patients. It is hoped that the complexes under investigation in this study will be selective for breast cancer cells and also be effective at low doses to maintain quality of life for patients undergoing treatment.
1. In vitro cytotoxicity, cellular uptake, reactive oxygen species and cell cycle arrest studies of novel ruthenium (II) polypyridyl complexes towards A549 human non-small cells lung cancer cell lines. Muhammad Qasim Mushtaq Warraich , Alessandra Ghion , Laura Perdisatt, Luke O’Neil1, Alan Casey, Christine O’Connor, Drug and Chemical Toxicology, 2019, DOI: 10.1080/01480545.2019.1589492.
2. Structure property relationships for a series of Ruthenium(II) Polypyridyl Complexes elucidated through systematic functional group change, by Luke O’Neill, Laura Perdisatt and Christine O’Connor submitted to Journal of Spectroscopy, Journal of Spectroscopy 2018(8):1-11 DOI: 10.1155/2018/3827130
3. Synthesis, characterization and DNA intercalation studies of regioisomers of ruthenium(II) polypyridyl complexes, L. Perdisatt, L. O’Neill, G. Hessman, S. Moqadasi, Q. Warraich, A. Ghion, A. Casey, C. O’Connor, Journal of Inorganic Biochemistry, 2018, 182, 71-82.
4. Influence of Auxiliary Ligands on the Photophysical Characteristics of a Series of Ruthenium(II)–Polypyridyl Complexes, L. O’Neill, L. Perdisatt and C. O’Connor, J. Phys. Chem. A, 2012, 116 (44), 10728–10735.

Student requirements for this project
A min. 2.1 (Hons) BSc in Biological Sciences, BSc in Medicinal Chemistry or related disciplines.
Some experience in cell culture or cytotoxicity studies would be an advantage.

Self-Funded (Scholarship not available. Fees & Materials to be paid by the student. Materials costs not significant)
www.tudublin.ie/research/phd-research-opportunities/phd-registration-fees/

If you are interested in submitting an application for this project, please complete an Expression of Interest (www.dit.ie/media/documents/study/postgraduateresearch/EOI%20Form.doc)and email it to [email protected]