Breaking photoswitch activation depth limit using ionising radiation stimuli adapted to clinical application

Alban Guesdon-Vennerie, Patrick Couvreur, Fatoumia Ali, Frédéric Pouzoulet, Christophe Roulin, Immaculada Martínez-Rovira, Guillaume Bernadat, François-Xavier Legrand, Claudie Bourgaux, Cyril Lucien Mazars, Sergio Marco, Sylvain Trépout, Simona Mura, Sébastien Mériaux and Guillaume Bort ()
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Alban Guesdon-Vennerie: Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay
Patrick Couvreur: Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay
Fatoumia Ali: Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay
Frédéric Pouzoulet: Institut Curie, PSL Research University, Translational Research Department, Experimental Radiotherapy Platform, UMR 1288
Christophe Roulin: Institut Curie, PSL Research University, Translational Research Department, Experimental Radiotherapy Platform, UMR 1288
Immaculada Martínez-Rovira: Universitat Autònoma de Barcelona
Guillaume Bernadat: Université Paris-Saclay, CNRS, BioCIS
François-Xavier Legrand: Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay
Claudie Bourgaux: Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay
Cyril Lucien Mazars: Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay
Sergio Marco: Institut Curie, Université Paris-Saclay, CNRS UMR9187
Sylvain Trépout: Institut Curie, Université Paris-Saclay, CNRS UMR9187
Simona Mura: Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay
Sébastien Mériaux: Université Paris-Saclay, CEA, CNRS, BAOBAB, NeuroSpin
Guillaume Bort: Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Electromagnetic radiation-triggered therapeutic effect has attracted a great interest over the last 50 years. However, translation to clinical applications of photoactive molecular systems developed to date is dramatically limited, mainly because their activation requires excitation by low-energy photons from the ultraviolet to near infra-red range, preventing any activation deeper than few millimetres under the skin. Herein we conceive a strategy for photosensitive-system activation potentially adapted to biological tissues without any restriction in depth. High-energy stimuli, such as those employed for radiotherapy, are used to carry energy while molecular activation is provided by local energy conversion. This concept is applied to azobenzene, one of the most established photoswitches, to build a radioswitch. The radiation-responsive molecular system developed is used to trigger cytotoxic effect on cancer cells upon gamma-ray irradiation. This breakthrough activation concept is expected to expand the scope of applications of photosensitive systems and paves the way towards the development of original therapeutic approaches.

Date: 2022
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DOI: 10.1038/s41467-022-30917-0

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