Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors
Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance to conventional therapies, leading to poor patient outcomes. This challenges the efficiency of photodynamic therapy (PDT), which relies on the generation of cytotoxic reactive oxygen sp...
| Autores: | , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| 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:20.500.14342/5500 |
| Acceso en línea: | http://hdl.handle.net/20.500.14342/5500 https://doi.org/10.1021/jacs.4c15036 |
| Access Level: | acceso abierto |
| Palabra clave: | Electromagnetic radiation Irradiation Ligands Light Oxygen Electromagnetisme Irradiació Lligands (Bioquímica) Llum Oxigen 537 577 |
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ES_e5d05fb87e2bac203dfd3026ffca7f27 |
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oai:recercat.cat:20.500.14342/5500 |
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España |
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Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors Abad-Montero, Diego Gandioso, Albert Izquierdo García, Eduardo Chumillas, Sergi Rovira, Anna Bosch, Manel Jordà-Redondo, Mireia Castaño, Davor Bonelli, Joaquín Novikov, Valentin Deyà, Alba Hernández, José Luis Galino, Jorge Alberto, Marta Erminia Francés-Monerris, Antonio Nonell, Santi Gasser, Gilles Marchán, Vicente Electromagnetic radiation Irradiation Ligands Light Oxygen Electromagnetisme Irradiació Lligands (Bioquímica) Llum Oxigen 537 577 Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance to conventional therapies, leading to poor patient outcomes. This challenges the efficiency of photodynamic therapy (PDT), which relies on the generation of cytotoxic reactive oxygen species (ROS) through the irradiation of a photosensitizer (PS), a process partially dependent on oxygen levels. In this work, we introduce a novel family of potent PSs based on ruthenium(II) polypyridyl complexes with 2,2′-bipyridyl ligands derived from COUPY coumarins, termed COUBPYs. Ru-COUBPY complexes exhibit outstanding in vitro cytotoxicity against CT-26 cancer cells when irradiated with light within the phototherapeutic window, achieving nanomolar potency in both normoxic and hypoxic conditions while remaining nontoxic in the dark, leading to impressive phototoxic indices (>30,000). Their ability to generate both Type I and Type II ROS underpins their exceptional PDT efficiency. The lead compound of this study, SCV49, shows a favorable in vivo pharmacokinetic profile, excellent toxicological tolerability, and potent tumor growth inhibition in mice bearing subcutaneous CT-26 tumors at doses as low as 3 mg/kg upon irradiation with deep-red light (660 nm). These results allow us to propose SCV49 as a strong candidate for further preclinical development, particularly for treating large hypoxic solid tumors. info:eu-repo/semantics/publishedVersion American Chemical Society http://hdl.handle.net/20.500.14342/5500 https://doi.org/10.1021/jacs.4c15036 |
| title |
Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors |
| spellingShingle |
Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors Abad-Montero, Diego Electromagnetic radiation Irradiation Ligands Light Oxygen Electromagnetisme Irradiació Lligands (Bioquímica) Llum Oxigen 537 577 |
| title_short |
Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors |
| title_full |
Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors |
| title_fullStr |
Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors |
| title_full_unstemmed |
Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors |
| title_sort |
Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors |
| author |
Abad-Montero, Diego |
| author_facet |
Abad-Montero, Diego Gandioso, Albert Izquierdo García, Eduardo Chumillas, Sergi Rovira, Anna Bosch, Manel Jordà-Redondo, Mireia Castaño, Davor Bonelli, Joaquín Novikov, Valentin Deyà, Alba Hernández, José Luis Galino, Jorge Alberto, Marta Erminia Francés-Monerris, Antonio Nonell, Santi Gasser, Gilles Marchán, Vicente |
| author_role |
author |
| author2 |
Gandioso, Albert Izquierdo García, Eduardo Chumillas, Sergi Rovira, Anna Bosch, Manel Jordà-Redondo, Mireia Castaño, Davor Bonelli, Joaquín Novikov, Valentin Deyà, Alba Hernández, José Luis Galino, Jorge Alberto, Marta Erminia Francés-Monerris, Antonio Nonell, Santi Gasser, Gilles Marchán, Vicente |
| author2_role |
author author author author author author author author author author author author author author author author author |
| topic |
Electromagnetic radiation Irradiation Ligands Light Oxygen Electromagnetisme Irradiació Lligands (Bioquímica) Llum Oxigen 537 577 |
| topic_facet |
Electromagnetic radiation Irradiation Ligands Light Oxygen Electromagnetisme Irradiació Lligands (Bioquímica) Llum Oxigen 537 577 |
| description |
Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance to conventional therapies, leading to poor patient outcomes. This challenges the efficiency of photodynamic therapy (PDT), which relies on the generation of cytotoxic reactive oxygen species (ROS) through the irradiation of a photosensitizer (PS), a process partially dependent on oxygen levels. In this work, we introduce a novel family of potent PSs based on ruthenium(II) polypyridyl complexes with 2,2′-bipyridyl ligands derived from COUPY coumarins, termed COUBPYs. Ru-COUBPY complexes exhibit outstanding in vitro cytotoxicity against CT-26 cancer cells when irradiated with light within the phototherapeutic window, achieving nanomolar potency in both normoxic and hypoxic conditions while remaining nontoxic in the dark, leading to impressive phototoxic indices (>30,000). Their ability to generate both Type I and Type II ROS underpins their exceptional PDT efficiency. The lead compound of this study, SCV49, shows a favorable in vivo pharmacokinetic profile, excellent toxicological tolerability, and potent tumor growth inhibition in mice bearing subcutaneous CT-26 tumors at doses as low as 3 mg/kg upon irradiation with deep-red light (660 nm). These results allow us to propose SCV49 as a strong candidate for further preclinical development, particularly for treating large hypoxic solid tumors. |
| publishDate |
2025 |
| format |
article |
| url |
http://hdl.handle.net/20.500.14342/5500 https://doi.org/10.1021/jacs.4c15036 |
| eu_rights_str_mv |
openAccess |
| publisher |
American Chemical Society |
| institution |
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| collection |
Recercat. Dipósit de la Recerca de Catalunya |
| reponame_str |
Recercat. Dipósit de la Recerca de Catalunya |
| instname_str |
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| _version_ |
1878442176227049472 |
| publishDateSort |
2025 |
| author_browse |
Abad-Montero, Diego Alberto, Marta Erminia Bonelli, Joaquín Bosch, Manel Castaño, Davor Chumillas, Sergi Deyà, Alba Francés-Monerris, Antonio Galino, Jorge Gandioso, Albert Gasser, Gilles Hernández, José Luis Izquierdo García, Eduardo Jordà-Redondo, Mireia Marchán, Vicente Nonell, Santi Novikov, Valentin Rovira, Anna |
| publisherStr |
American Chemical Society |
| score |
6,9303427 |