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:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu: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 Chemistry2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/201946Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció 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:diposit.ub.edu:2445/2019462026-05-27T06:46:51Z
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
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 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:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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