Ru(II)‐Cyanine Complexes as Promising Photodynamic Photosensitizers for the Treatment of Hypoxic Tumours with Highly Penetrating 770 nm Near‐Infrared Light

Light‐activated treatments, such as photodynamic therapy (PDT), provide temporal and spatial control over a specific cytotoxic response by exploiting toxicity differences between irradiated and dark conditions. In this work, a novel strategy for developing near infrared (NIR)‐activatable Ru(II) polypyridyl‐based photosensitizers (PSs) was successfully developed through the incorporation of symmetric heptamethine cyanine dyes in the metal complex via a phenanthrimidazole ligand. Owing to their strong absorption in the NIR region, the PSs could be efficiently photoactivated with highly penetrating NIR light (770 nm), leading to high photocytotoxicities towards several cancer cell lines under both normoxic and hypoxic conditions. Notably, our lead PS (Ru‐Cyn‐1), which accumulated in the mitochondria, exhibited a good photocytotoxic activity under challenging low‐oxygen concentration (2% O2) upon NIR light irradiation conditions (770 nm), owing to a combination of types I and II PDT mechanism. The fact that the PS Protoporphyrin IX (PpIX), the metabolite of the clinically approved 5‐ALA PS, was found inactive under the same challenging conditions positions Ru‐Cyn‐1 complex as a promising PDT agent for the treatment of deep‐seated hypoxic tumours.

Mots clés

cyanine medicinal inorganic chemistry photodynamic therapy photosensitizer ruthenium(II) complexes

Domaines

Chimie thérapeutique Chimie de coordination

Liste complète des métadonnées

Format du dépôt	Fichier
Type de dépôt	Article dans une revue
Titre	en Ru(II)‐Cyanine Complexes as Promising Photodynamic Photosensitizers for the Treatment of Hypoxic Tumours with Highly Penetrating 770 nm Near‐Infrared Light
Résumé	en Light‐activated treatments, such as photodynamic therapy (PDT), provide temporal and spatial control over a specific cytotoxic response by exploiting toxicity differences between irradiated and dark conditions. In this work, a novel strategy for developing near infrared (NIR)‐activatable Ru(II) polypyridyl‐based photosensitizers (PSs) was successfully developed through the incorporation of symmetric heptamethine cyanine dyes in the metal complex via a phenanthrimidazole ligand. Owing to their strong absorption in the NIR region, the PSs could be efficiently photoactivated with highly penetrating NIR light (770 nm), leading to high photocytotoxicities towards several cancer cell lines under both normoxic and hypoxic conditions. Notably, our lead PS (Ru‐Cyn‐1), which accumulated in the mitochondria, exhibited a good photocytotoxic activity under challenging low‐oxygen concentration (2% O2) upon NIR light irradiation conditions (770 nm), owing to a combination of types I and II PDT mechanism. The fact that the PS Protoporphyrin IX (PpIX), the metabolite of the clinically approved 5‐ALA PS, was found inactive under the same challenging conditions positions Ru‐Cyn‐1 complex as a promising PDT agent for the treatment of deep‐seated hypoxic tumours.
Auteur(s)	Albert Gandioso ¹ , Eduardo Izquierdo-García ¹ , Pierre Mesdom ¹ , Philippe Arnoux ² , Nurikamal Demeubayeva ² , Pierre Burckel ³ , Bruno Saubaméa ⁴ , Manel Bosch ⁵ , Céline Frochot ² , Vicente Marchán ⁵ , Gilles Gasser ¹ 1 ENSCP - Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL ( 300372 ) - 11, rue Pierre et Marie Curie 75231 Paris Cedex 05 - France Université Paris Sciences et Lettres ( 564132 ) 2 LRGP - Laboratoire Réactions et Génie des Procédés ( 211875 ) - Université de Lorraine - ENSIC, 1 rue de Grandville BP 20451, 54001 Nancy Cedex - France Université de Lorraine ( 413289 ) ; Centre National de la Recherche Scientifique UMR7274 / UPR3349 ( 441569 ) 3 IPGP (UMR_7154) - Institut de Physique du Globe de Paris ( 1005035 ) - 1 rue Jussieu, 75238 Paris cedex 05 et Bât. Lamarck A case postale 7011, 75205 Paris CEDEX 13 - France Institut national des sciences de l'Univers UMR_7154 ( 300045 ) ; Université de La Réunion UMR_7154 ( 300316 ) ; Institut de Physique du Globe de Paris UMR_7154 ( 300354 ) ; Centre National de la Recherche Scientifique UMR_7154 ( 441569 ) ; Université Paris Cité UMR_7154 ( 557826 ) 4 P-MIM - UMS 3612 - Plates-formes mutualisées du centre de recherche pharmaceutique de Paris ( 1004697 ) - Faculté de pharmacie de Paris - Université Paris Descartes 4 Avenue de l'Observatoire 75006 Paris - France Institut de Recherche pour le Développement UMS3612 ( 67872 ) ; Institut National de la Santé et de la Recherche Médicale US25 ( 303623 ) ; Institut de Chimie - CNRS Chimie ( 341038 ) ; Centre National de la Recherche Scientifique UAR3612 ( 441569 ) ; Université Paris Cité UMS3612 ( 557826 ) 5 UB - Universitat de Barcelona ( 3447 ) - Gran Via de les Corts Catalanes, 585, 08007 Barcelona - Espagne
Vulgarisation	Non
Comité de lecture	Oui
Audience	Internationale
Date de publication électronique	2023-08-07
Date de publication	2023-11
Volume	29
Numéro	61
Page/Identifiant	e202301742
Langue du document	Anglais
Nom de la revue	Chemistry - A European Journal (ISSN : 0947-6539, ISSN électronique : 1521-3765) Wiley-VCH Verlag Publié par Wiley-VCH Verlag hhtp://www3.interscience.wiley.com/cgi-bin/jhome/26293/
Projet(s) Européen(s)	PhotoMedMet - Towards Novel Inert (Photo-)toxic Ru(II) Polypyridyl Complexes Numéro CORDIS : 681679
Financement	ERC Grant ERC Grant
Domaine(s)	Chimie/Chimie thérapeutique Chimie/Chimie de coordination
Projet(s) ANR	Paris Sciences et Lettres [En savoir plus] PSL - ANR-10-IDEX-0001 IDEX - 2010
Mots-clés	en cyanine, medicinal inorganic chemistry, photodynamic therapy, photosensitizer, ruthenium(II) complexes
DOI	10.1002/chem.202301742

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Soumis le : vendredi 18 août 2023 à 17:11:32

Dernière modification le : lundi 23 septembre 2024 à 16:18:24

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hal-04183197, version 1 (18-08-2023)

Identifiants

HAL Id : hal-04183197 , version 1
DOI : 10.1002/chem.202301742

Citer

Albert Gandioso, Eduardo Izquierdo-García, Pierre Mesdom, Philippe Arnoux, Nurikamal Demeubayeva, et al.. Ru(II)‐Cyanine Complexes as Promising Photodynamic Photosensitizers for the Treatment of Hypoxic Tumours with Highly Penetrating 770 nm Near‐Infrared Light. Chemistry - A European Journal, 2023, 29 (61), pp.e202301742. ⟨10.1002/chem.202301742⟩. ⟨hal-04183197⟩

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