Thesis defence

Hélène MOULET

Tuesday 05 February 2019 at 2.00 pm
Campus Cité Scientifique, Bât. P5, Amphithéâtre Pierre Glorieux

Jury:

• Stéphanie BONNEAU (Pierre and Marie Curie University, Rapporteur),
• CélineFROCHOTt (University of Lorraine, Rapporteur)
• Peter OGILBY (University of Aarhus, Examiner)
• Marc DOUAY (University of Lille, Examiner)
• Emmanuel COURTADE (University of Lille, thesis supervisor)
• Anthony TREIZEBRE (University of Lille, co-supervisor)

Summary:

Singlet oxygen (1O2), the first excited electronic state of oxygen, is the major cytotoxic agent in photodynamic therapy. We used direct optical activation of dioxygen to establish a quantitative link between the rate of 1O2 production and cell death.

In tumour spheroids, which reproduce the geometry of tumours in vitro, we demonstrate long-range cell death that cannot be explained by the direct action of 1O2. This death is due to 1O2 produced within the spheroids but outside the cells. We have set up an experiment that allows us to spatially control the production of 1O2 outside the cells. The cell death observed at long range in these experiments involves the presence of secondary reactive oxygen species.

Finally, certain types of death are preferred from a therapeutic point of view, in order to limit the inflammatory response, among other things. We have set up an in vitro experiment that allows us to observe different modes of death as a function of the rate of 1O2 production and the exposure time.

Abstract:

Singlet oxygen (1O2) is the first excited state of molecular oxygen. It is the major cytotoxic agent in photo dynamic therapy. We use direct optical excitation of oxygen to quantitatively estimate 1O2 production rate in cells and to study its cytotoxic effects.

In multicellular tumor spheroids, which mimic tumor geometry in vitro, we highlight longrange cell death that cannot be explained by singlet oxygen alone. This death is caused by 1O2 generated within spheroids but outside of the cells. We set up an experiment enabling spatial control of extra-cellular 1O2 production. The measured long-range cell death in these experiments implies the presence of secondary reactive oxygen species.

Lastly, some cell death modalities are preferred from a treatment perspective, in order, for example, to limit inflammatory response. We set up an experiment that enabled us to observe different cell death modalities according to 1O2 production rates and exposure times.