After its launch last year, the ISIS Impact Awards was again opened to facility users, celebrating the scientific, social and economic impact generated by the user community. The winner of the Society Award was Professor Maria Paula M. Marques, the co-coordinator of the Molecular Physical-Chemistry R&D Unit of Coimbra University, Portugal. The Unit's main goal is the development of improved platinum and palladium-based anticancer agents for low prognosis cancers, for which no successful therapeutic strategies are available.
Professor Marques and her team use neutron scattering techniques (inelastic and quasi-elastic) to study the changes happening inside the cell as it undergoes drug treatment. Their work focusses on the water inside the cell, and how this 'intracellular water' could be used as a target for anticancer drugs.
The water inside the cells has different properties to water outside the body – it maintains the three-dimensional architecture and functional conformation of the molecules required for normal cellular activity. Just small variations in the structure or dynamics of intracellular water could trigger inhibition of cell growth and eventually cell death.
The team used inelastic and quasi-elastic neutron scattering (QENS) techniques as a direct probe of the behaviour of the different types of cellular water, in the presence and absence of a drug. For these experiments, the team developed a new experimental procedure where cells were grown and drug-incubated immediately before neutron data acquisition.
The measurements (QENS with isotope labelling) were very successful in highlighting drug-induced differences in intracellular water mobility. These studies constitute an innovative approach for chemotherapeutic research, aiding the interpretation of a drug´s mode of action within the cell and enabling the identification of alternative therapeutic targets. Looking at water as a promising chemotherapeutic target may pave the way for the development of improved anti-tumour drugs with multiple sites of action, i.e. multi-targeted as opposed to single-targeted agents, leading to an enhanced efficiency and minimised acquired resistance during treatment.
Media interest:
- Several articles in portuguese and spanish newspapers (2015-2018);
- live interview for Porto Canal – Mentes que Brilham (23th April 2014) (http://bit.ly/2hRgurU);
- interview for the BBC World Service – Science in Action (12th November 2015)
Published articles:
1. Anticancer Drug Impact on DNA – A Study by Neutron Spectroscopy coupled to Synchrotron-based FTIR and EXAFS, A.L.M. Batista de Carvalho, A.P. Mamede, A. Dopplapudi, V. Garcia Sakai, J. Doherty, M. Frogley, G. Cinque, P. Gardner, D. Gianolio, L.A.E. Batista de Carvalho, M.P.M. Marques, Phys.Chem.Chem.Phys. 21 (2019) 4162 (DOI: 10.1039/C8CP05881D).
2. Intracellular Water – an Overlooked Drug Target? Cisplatin´s Impact in Cancer Cells Probed by Neutrons, M.P.M. Marques, A.L.M. Batista de Carvalho, V. Garcia-Sakai, L. Hatter, L.A.E. Batista de Carvalho, Phys.Chem.Chem.Phys. 19 (2017) 2702 (DOI: 10.1039/C6CP05198G). The first article on the drug impact on intracellular water featured on the back cover of Phys.Chem.Chem.Phys. (19 (2017) 2702, DOI 10.1039/C6CP05198G)
Submitted articles:
1. Intracellular Water as a Mediator of Anticancer Drug Action, M.P.M. Marques, A.L.M. Batista de Carvalho, A.P Mamede, A. Dopplapudi, V. García Sakai and L.A.E. Batista de Carvalho, Cancer Lett.
2. Chemotherapeutic Targets in Osteosarcoma – Insights from Synchrotron-microFTIR and Quasi-elastic Neutron Scattering, M.P.M. Marques, A.L.M. Batista de Carvalho, A.P Mamede, I.P. Santos, V. García Sakai, A. Dopplapudi, G. Cinque, M. Wolna, P. Gardner, L.A.E. Batista de Carvalho, JACS."
