Claire DONOHOE

Project title: Photo-immunotherapy: potentiating the anti-tumour triggeres by photodynamic therapy

Employer: Universty of Coimbra (UC, Portugal), Cotutelle: Trinity College of Dublin (TCD, Ireland)
Supervisors: Dr. Ligia GOMES DA-SILVA (UC), Prof. Dr. Mathias O. SENGE (TCD)

ESR representative at the Supervisory Board (2018-2019)

Research secondments: BET Solutions, PorphyChem
Practical rotation: Biolitec

Research project description and main objectives: Atropisomerism presents an unexpected source of structural diversity in drug development. An awareness of the implications of this diversity for tetrapyrrole structures may enhance photosensitizer development for photodynamic therapy (PDT). The thesis project aims to investigate the efficacy of the atropisomers of a pre-clinical photosensitizer (PS), redaporfin, for PDT. This synthetic sulphonamide fluorinated bacteriochlorin presents suitable parameters for studying PDT including enhanced photostability, strong absorption at 750 nm and high ROS yields. Redaporfin is currently in clinical trials for head and neck cancer (NCT02070432). Its phenyl-macrocyclic single bonds experience hindered rotation. This results in different spatial distributions of the sulphonamide groups in the meta positions generating four distinct chemical species in the form of atropisomers. This project proposes that the different atropisomers of Redaporfin may have different photo-toxic activities. The best atropisomer will be further characterized in detail regarding its immunomodulatory properties, namely in the context of pseudo-metastatic mouse models. The project’s primary objective is to understand why the variation in toxicity exists and to exploit enhanced efficacy through atropisomer isolation and use in combination therapy for PDT.

Claire’s publications:

K. Norvaisa, S. Maguire, C. Donohoe, J.E. O’Brien, B. Twamley, L. C. Gomes-da-Silva, M. O. Senge, Steric Repulsion Induced Conformational Switch in Supramolecular Structures, Chemistry A European Journal, 2021, https://doi.org/10.1002/chem.202103879
P. Gierlich, A.I. Mata, C. Donohoe, R.M.M Brito, M.O. Senge, L.C. Gomes-da-Silva, Ligand-tageted delivery of photosensitizers for cancer treatment, MDPI, 2020, DOI: 10.3390/molecules25225317
C. Donohoe, M. O.Senge, L. G. Arnaut and L. C.Gomes-da-Silva, Cell death in photodynamic therapy: From oxidative stress to anti-tumor immunity, Biochimica et Biophysica Acta (BBA) – Reviews on Cancer, 2019, DOI: 10.1016/j.bbcan.2019.07.003

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