Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein

A primary objective of photodynamic therapy (PDT) is to develop tumor-targeted photosensitizers (PS) that enable selective cytotoxicity through preferential accumulation in cancer tissues and local activation by light. Here, we report on the synthesis of two novel Ir(III) PSs (1 and 2), designed wit...

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Autores: Zafon, Elisenda, Riesco-Llach, Gerard, Echevarría Poza, Igor, Martínez Alonso, Marta, Feliu Soley, Lidia, Espino, Gustavo, Massaguer i Vall-llovera, Anna
Tipo de recurso: artículo
Estado:Versión publicada
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:10256/27686
Acceso en línea:http://hdl.handle.net/10256/27686
Access Level:acceso abierto
Palabra clave:Càncer -- Tractament
Cancer -- Treatment
Fotoquimioteràpia
Photochemotherapy
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spelling Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluoresceinZafon, ElisendaRiesco-Llach, GerardEchevarría Poza, IgorMartínez Alonso, MartaFeliu Soley, LidiaEspino, GustavoMassaguer i Vall-llovera, AnnaCàncer -- TractamentCancer -- TreatmentFotoquimioteràpiaPhotochemotherapyA primary objective of photodynamic therapy (PDT) is to develop tumor-targeted photosensitizers (PS) that enable selective cytotoxicity through preferential accumulation in cancer tissues and local activation by light. Here, we report on the synthesis of two novel Ir(III) PSs (1 and 2), designed with a terminal alkynyl moiety for subsequent peptide conjugation via click chemistry. Both complexes demonstrated photocatalytic activity, efficiently generating singlet oxygen (1O2). Complex 1 also exhibited remarkable phototoxicity, achieving nanomolar IC50 values in several cancer cell lines following light exposure. Complex 1 accumulated mainly in mitochondria, where it triggered membrane depolarization and apoptosis upon photoactivation, without affecting the cell cycle. To enhance tumor selectivity, 1 was conjugated to different derivatives of the tumor-targeting peptide bombesin, yielding 13 metallopeptides. Although conjugation reduced the cytotoxicity of 1, some metallopeptides were 2–4 times more active against PC3 cancer cells than healthy fibroblasts, which confirmed their improved selectivity. A double-functionalized metallopeptide bearing both 1 and carboxyfluorescein (CF) at the N-terminal Lys (1-Tr-Lys(CF)-NLS-BN3) was synthesized. This molecular architecture exhibited emission quenching relative to the metal-free derivative (CF-NLS-BN3) and an enhanced photodynamic effect compared to the CF-free metallopeptide (1-Tr-Lys-NLS-BN3). Based on photophysical studies, both observations were rationalized as a result of a photoinduced electron transfer process. The synergistic effect between the Ir and the CF fragments, combined with the peptide-mediated selectivity, offers significant insights for optimizing metal-based PSs for cancer therapyThis work was supported by the by the Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación (MCIN/AEI) of Spain (projects PID2021-127187OB-C21 and PID2021-127187OB-C22/ MCIN/ AEI / 10.13039/501100011033/FEDER, UE). PhD students acknowledge their predoctoral grants to University of Girona (G.R., IFUdG2020) and Generalitat de Catalunya (E.Z., AGAUR; 2021 FI_B 01036). Open Access funding was provided thanks to the CRUE-CSIC agreement with ElsevierElsevierAgencia Estatal de Investigación2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/27686Bioorganic Chemistry, 2025, vol. 166, art. núm. 109142Articles publicats (D-B)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bioorg.2025.109142info:eu-repo/semantics/altIdentifier/issn/0045-2068info:eu-repo/semantics/altIdentifier/eissn/1090-2120PID2021-127187OB-C22info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C22Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/276862026-05-29T05:05:01Z
dc.title.none.fl_str_mv Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein
title Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein
spellingShingle Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein
Zafon, Elisenda
Càncer -- Tractament
Cancer -- Treatment
Fotoquimioteràpia
Photochemotherapy
title_short Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein
title_full Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein
title_fullStr Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein
title_full_unstemmed Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein
title_sort Photoinduced electron transfer enhances the tumor-targeted photodynamic activity of bombesin metallopeptides incorporating an Ir(III) complex and carboxyfluorescein
dc.creator.none.fl_str_mv Zafon, Elisenda
Riesco-Llach, Gerard
Echevarría Poza, Igor
Martínez Alonso, Marta
Feliu Soley, Lidia
Espino, Gustavo
Massaguer i Vall-llovera, Anna
author Zafon, Elisenda
author_facet Zafon, Elisenda
Riesco-Llach, Gerard
Echevarría Poza, Igor
Martínez Alonso, Marta
Feliu Soley, Lidia
Espino, Gustavo
Massaguer i Vall-llovera, Anna
author_role author
author2 Riesco-Llach, Gerard
Echevarría Poza, Igor
Martínez Alonso, Marta
Feliu Soley, Lidia
Espino, Gustavo
Massaguer i Vall-llovera, Anna
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación
dc.subject.none.fl_str_mv Càncer -- Tractament
Cancer -- Treatment
Fotoquimioteràpia
Photochemotherapy
topic Càncer -- Tractament
Cancer -- Treatment
Fotoquimioteràpia
Photochemotherapy
description A primary objective of photodynamic therapy (PDT) is to develop tumor-targeted photosensitizers (PS) that enable selective cytotoxicity through preferential accumulation in cancer tissues and local activation by light. Here, we report on the synthesis of two novel Ir(III) PSs (1 and 2), designed with a terminal alkynyl moiety for subsequent peptide conjugation via click chemistry. Both complexes demonstrated photocatalytic activity, efficiently generating singlet oxygen (1O2). Complex 1 also exhibited remarkable phototoxicity, achieving nanomolar IC50 values in several cancer cell lines following light exposure. Complex 1 accumulated mainly in mitochondria, where it triggered membrane depolarization and apoptosis upon photoactivation, without affecting the cell cycle. To enhance tumor selectivity, 1 was conjugated to different derivatives of the tumor-targeting peptide bombesin, yielding 13 metallopeptides. Although conjugation reduced the cytotoxicity of 1, some metallopeptides were 2–4 times more active against PC3 cancer cells than healthy fibroblasts, which confirmed their improved selectivity. A double-functionalized metallopeptide bearing both 1 and carboxyfluorescein (CF) at the N-terminal Lys (1-Tr-Lys(CF)-NLS-BN3) was synthesized. This molecular architecture exhibited emission quenching relative to the metal-free derivative (CF-NLS-BN3) and an enhanced photodynamic effect compared to the CF-free metallopeptide (1-Tr-Lys-NLS-BN3). Based on photophysical studies, both observations were rationalized as a result of a photoinduced electron transfer process. The synergistic effect between the Ir and the CF fragments, combined with the peptide-mediated selectivity, offers significant insights for optimizing metal-based PSs for cancer therapy
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/27686
url http://hdl.handle.net/10256/27686
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bioorg.2025.109142
info:eu-repo/semantics/altIdentifier/issn/0045-2068
info:eu-repo/semantics/altIdentifier/eissn/1090-2120
PID2021-127187OB-C22
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C22
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Bioorganic Chemistry, 2025, vol. 166, art. núm. 109142
Articles publicats (D-B)
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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