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

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.

SUBMITTER: Guesdon-Vennerie A

PROVIDER: S-EPMC9283480 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Guesdon-Vennerie Alban A Couvreur Patrick P Ali Fatoumia F Pouzoulet Frédéric F Roulin Christophe C Martínez-Rovira Immaculada I Bernadat Guillaume G Legrand François-Xavier FX Bourgaux Claudie C Mazars Cyril Lucien CL Marco Sergio S Trépout Sylvain S Mura Simona S Mériaux Sébastien S Bort Guillaume G

Nature communications 20220714 1

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 ...[more]

PMID: 35835744

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Project description:ObjectiveTo systematically review and perform a meta-analysis of radiation associated risks of cardiovascular disease in all groups exposed to radiation with individual radiation dose estimates.DesignSystematic review and meta-analysis.Main outcome measuresExcess relative risk per unit dose (Gy), estimated by restricted maximum likelihood methods.Data sourcesPubMed and Medline, Embase, Scopus, Web of Science Core collection databases.Eligibility criteria for selecting studiesDatabases were searched on 6 October 2022, with no limits on date of publication or language. Animal studies and studies without an abstract were excluded.ResultsThe meta-analysis yielded 93 relevant studies. Relative risk per Gy increased for all cardiovascular disease (excess relative risk per Gy of 0.11 (95% confidence interval 0.08 to 0.14)) and for the four major subtypes of cardiovascular disease (ischaemic heart disease, other heart disease, cerebrovascular disease, all other cardiovascular disease). However, interstudy heterogeneity was noted (P<0.05 for all endpoints except for other heart disease), possibly resulting from interstudy variation in unmeasured confounders or effect modifiers, which is markedly reduced if attention is restricted to higher quality studies or those at moderate doses (<0.5 Gy) or low dose rates (<5 mGy/h). For ischaemic heart disease and all cardiovascular disease, risks were larger per unit dose for lower dose (inverse dose effect) and for fractionated exposures (inverse dose fractionation effect). Population based excess absolute risks are estimated for a number of national populations (Canada, England and Wales, France, Germany, Japan, USA) and range from 2.33% per Gy (95% confidence interval 1.69% to 2.98%) for England and Wales to 3.66% per Gy (2.65% to 4.68%) for Germany, largely reflecting the underlying rates of cardiovascular disease mortality in these populations. Estimated risk of mortality from cardiovascular disease are generally dominated by cerebrovascular disease (around 0.94-1.26% per Gy), with the next largest contribution from ischaemic heart disease (around 0.30-1.20% per Gy).ConclusionsResults provide evidence supporting a causal association between radiation exposure and cardiovascular disease at high dose, and to a lesser extent at low dose, with some indications of differences in risk between acute and chronic exposures, which require further investigation. The observed heterogeneity complicates a causal interpretation of these findings, although this heterogeneity is much reduced if only higher quality studies or those at moderate doses or low dose rates are considered. Studies are needed to assess in more detail modifications of radiation effect by lifestyle and medical risk factors.Systematic review registrationPROSPERO CRD42020202036.

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

Publications

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

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