A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions

Ortega Forte, Enrique; Rovira, Anna; López-Corrales, Marta; Hernández-García, Alba; Ballester, Francisco José; Izquierdo García, Eduardo; Bosch Marimon, Manel; Nonell, Santi; Santana, María Dolores; Ruiz, José; Marchán Sancho, Vicente; Gasser, Gilles; Jordà-Redondo, Mireia

A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions

Photodynamic therapy (PDT) represents a promising approach for cancer treatment. However, the oxygen dependency of PDT to generate reactive oxygen species (ROS) hampers its therapeutic efficacy, especially against hypoxic solid tumors. In addition, some photosensitizers (PSs) have dark toxicity and...

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Autores:	Ortega Forte, Enrique, Rovira, Anna, López-Corrales, Marta, Hernández-García, Alba, Ballester, Francisco José, Izquierdo García, Eduardo, Bosch Marimon, Manel, Nonell, Santi, Santana, María Dolores, Ruiz, José, Marchán Sancho, Vicente, Gasser, Gilles, Jordà-Redondo, Mireia
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2023
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/201946
Acceso en línea:	https://hdl.handle.net/2445/201946
Access Level:	acceso abierto
Palabra clave:	Cumarines Tumors Ruteni Coumarins Ruthenium

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spelling	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditionsOrtega Forte, EnriqueRovira, AnnaLópez-Corrales, MartaHernández-García, AlbaBallester, Francisco JoséIzquierdo García, EduardoBosch Marimon, ManelNonell, SantiSantana, María DoloresRuiz, JoséMarchán Sancho, VicenteGasser, GillesJordà-Redondo, MireiaCumarinesTumorsRuteniCoumarinsTumorsRutheniumPhotodynamic therapy (PDT) represents a promising approach for cancer treatment. However, the oxygen dependency of PDT to generate reactive oxygen species (ROS) hampers its therapeutic efficacy, especially against hypoxic solid tumors. In addition, some photosensitizers (PSs) have dark toxicity and are only activatable with short wavelengths such as blue or UV-light, which suffer from poor tissue penetration. Herein, we developed a novel hypoxia-active PS with operability in the near-infrared (NIR) region based on the conjugation of a cyclometalated Ru(II) polypyridyl complex of the type [Ru(C^N)(N^N)2] to a NIR-emitting COUPY dye. The novel Ru(II)-coumarin conjugate exhibits water-solubility, dark stability in biological media and high photostability along with advantageous luminescent properties that facilitate both bioimaging and phototherapy. Spectroscopic and photobiological studies revealed that this conjugate efficiently generates singlet oxygen and superoxide radical anions, thereby achieving high photoactivity toward cancer cells upon highly-penetrating 740 nm light irradiation even under hypoxic environments (2% O2). The induction of ROS-mediated cancer cell death upon low-energy wavelength irradiation along with the low dark toxicity exerted by this Ru(II)-coumarin conjugate could circumvent tissue penetration issues while alleviating the hypoxia limitation of PDT. As such, this strategy could pave the way to the development of novel NIR- and hypoxia-active Ru(II)-based theragnostic PSs fuelled by the conjugation of tunable, low molecular-weight COUPY fluorophores.Royal Society of Chemistry2023202320232023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfhttps://hdl.handle.net/2445/201946Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1039/D3SC01844JChemical Science, 2023, vol. 14, num. 26, p. 7170-7184https://doi.org/10.1039/D3SC01844Jcc-by-nc (c) Ortega-Forte, Enrique et al., 2023http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2019462026-05-29T05:05:01Z
dc.title.none.fl_str_mv	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions
title	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions
spellingShingle	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions Ortega Forte, Enrique Cumarines Tumors Ruteni Coumarins Tumors Ruthenium
title_short	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions
title_full	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions
title_fullStr	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions
title_full_unstemmed	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions
title_sort	A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions
dc.creator.none.fl_str_mv	Ortega Forte, Enrique Rovira, Anna López-Corrales, Marta Hernández-García, Alba Ballester, Francisco José Izquierdo García, Eduardo Bosch Marimon, Manel Nonell, Santi Santana, María Dolores Ruiz, José Marchán Sancho, Vicente Gasser, Gilles Jordà-Redondo, Mireia
author	Ortega Forte, Enrique
author_facet	Ortega Forte, Enrique Rovira, Anna López-Corrales, Marta Hernández-García, Alba Ballester, Francisco José Izquierdo García, Eduardo Bosch Marimon, Manel Nonell, Santi Santana, María Dolores Ruiz, José Marchán Sancho, Vicente Gasser, Gilles Jordà-Redondo, Mireia
author_role	author
author2	Rovira, Anna López-Corrales, Marta Hernández-García, Alba Ballester, Francisco José Izquierdo García, Eduardo Bosch Marimon, Manel Nonell, Santi Santana, María Dolores Ruiz, José Marchán Sancho, Vicente Gasser, Gilles Jordà-Redondo, Mireia
author2_role	author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Cumarines Tumors Ruteni Coumarins Tumors Ruthenium
topic	Cumarines Tumors Ruteni Coumarins Tumors Ruthenium
description	Photodynamic therapy (PDT) represents a promising approach for cancer treatment. However, the oxygen dependency of PDT to generate reactive oxygen species (ROS) hampers its therapeutic efficacy, especially against hypoxic solid tumors. In addition, some photosensitizers (PSs) have dark toxicity and are only activatable with short wavelengths such as blue or UV-light, which suffer from poor tissue penetration. Herein, we developed a novel hypoxia-active PS with operability in the near-infrared (NIR) region based on the conjugation of a cyclometalated Ru(II) polypyridyl complex of the type [Ru(C^N)(N^N)2] to a NIR-emitting COUPY dye. The novel Ru(II)-coumarin conjugate exhibits water-solubility, dark stability in biological media and high photostability along with advantageous luminescent properties that facilitate both bioimaging and phototherapy. Spectroscopic and photobiological studies revealed that this conjugate efficiently generates singlet oxygen and superoxide radical anions, thereby achieving high photoactivity toward cancer cells upon highly-penetrating 740 nm light irradiation even under hypoxic environments (2% O2). The induction of ROS-mediated cancer cell death upon low-energy wavelength irradiation along with the low dark toxicity exerted by this Ru(II)-coumarin conjugate could circumvent tissue penetration issues while alleviating the hypoxia limitation of PDT. As such, this strategy could pave the way to the development of novel NIR- and hypoxia-active Ru(II)-based theragnostic PSs fuelled by the conjugation of tunable, low molecular-weight COUPY fluorophores.
publishDate	2023
dc.date.none.fl_str_mv	2023 2023 2023 2023
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/201946
url	https://hdl.handle.net/2445/201946
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1039/D3SC01844J Chemical Science, 2023, vol. 14, num. 26, p. 7170-7184 https://doi.org/10.1039/D3SC01844J
dc.rights.none.fl_str_mv	cc-by-nc (c) Ortega-Forte, Enrique et al., 2023 http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by-nc (c) Ortega-Forte, Enrique et al., 2023 http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	15 p. application/pdf
dc.publisher.none.fl_str_mv	Royal Society of Chemistry
publisher.none.fl_str_mv	Royal Society of Chemistry
dc.source.none.fl_str_mv	Articles publicats en revistes (Química Inorgànica i Orgànica) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,811543

A near-infrared light-activatable Ru(II)-coumarin photosensitizer active under hypoxic conditions

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