Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy
One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes...
| Autores: | , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/380948 |
| Acceso en línea: | http://hdl.handle.net/10261/380948 |
| Access Level: | acceso abierto |
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Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy |
| title |
Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy |
| spellingShingle |
Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy Gonzalo-Navarro, Carlos |
| title_short |
Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy |
| title_full |
Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy |
| title_fullStr |
Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy |
| title_full_unstemmed |
Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy |
| title_sort |
Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy |
| dc.creator.none.fl_str_mv |
Gonzalo-Navarro, Carlos Zafon, Elisenda Organero, Juan Angel Jalón, Félix A. Lima, João Carlos Espino, Gustavo Rodríguez, Ana María Santos, Lucía Moro, Artur J. Barrabés, Sílvia Castro, Jessica Camacho-Aguayo, Javier Massaguer, Anna Manzano, Blanca R. Durá, Gema |
| author |
Gonzalo-Navarro, Carlos |
| author_facet |
Gonzalo-Navarro, Carlos Zafon, Elisenda Organero, Juan Angel Jalón, Félix A. Lima, João Carlos Espino, Gustavo Rodríguez, Ana María Santos, Lucía Moro, Artur J. Barrabés, Sílvia Castro, Jessica Camacho-Aguayo, Javier Massaguer, Anna Manzano, Blanca R. Durá, Gema |
| author_role |
author |
| author2 |
Zafon, Elisenda Organero, Juan Angel Jalón, Félix A. Lima, João Carlos Espino, Gustavo Rodríguez, Ana María Santos, Lucía Moro, Artur J. Barrabés, Sílvia Castro, Jessica Camacho-Aguayo, Javier Massaguer, Anna Manzano, Blanca R. Durá, Gema |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Agencia Estatal de Investigación (España) Ministerio de Ciencia, Innovación y Universidades (España) European Commission Junta de Comunidades de Castilla-La Mancha Junta de Castilla y León Fundação para a Ciência e a Tecnologia (Portugal) Universidad de Castilla La Mancha Universidad de Zaragoza Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| description |
One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1O2. We have obtained derivatives of formulas [Cp*Ir(C∧N)Cl] and [Cp*Ir(C∧N)L]BF4 with different degrees of π-expansion in the C∧N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Time-dependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of half-sandwich iridium cyclometalated complexes active in PDT. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/380948 |
| url |
http://hdl.handle.net/10261/380948 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C21 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C22 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105408GB-I00 Gonzalo-Navarro, Carlos; Zafon, Elisenda; Organero, Juan Angel; Jalón, Félix A.; Lima, João Carlos; Espino, Gustavo; Rodríguez, Ana María; Santos, Lucía; Moro, Artur J.; Barrabés, Sílvia; Castro, Jessica; Camacho-Aguayo, Javier; Massaguer, Anna; Manzano, Blanca R.; Durá, Gema; 2024; Supporting Information: Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy [Dataset]; American Chemical Society; https://doi.org/10.1021/acs.jmedchem.3c01276 https://doi.org/10.1021/acs.jmedchem.3c01276 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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American Chemical Society |
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American Chemical Society |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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1869419087221751808 |
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Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapyGonzalo-Navarro, CarlosZafon, ElisendaOrganero, Juan AngelJalón, Félix A.Lima, João CarlosEspino, GustavoRodríguez, Ana MaríaSantos, LucíaMoro, Artur J.Barrabés, SílviaCastro, JessicaCamacho-Aguayo, JavierMassaguer, AnnaManzano, Blanca R.Durá, GemaOne approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control of the cytotoxicity. We have used the strategy of coordinating π-expansive ligands to increase the excited state lifetimes of Ir(III) half-sandwich complexes in order to facilitate the generation of 1O2. We have obtained derivatives of formulas [Cp*Ir(C∧N)Cl] and [Cp*Ir(C∧N)L]BF4 with different degrees of π-expansion in the C∧N ligands. Complexes with the more π-expansive ligand are very effective photosensitizers with phototoxic indexes PI > 2000. Furthermore, PI values of 63 were achieved with red light. Time-dependent density functional theory (TD-DFT) calculations nicely explain the effect of the π-expansion. The complexes produce reactive oxygen species (ROS) at the cellular level, causing mitochondrial membrane depolarization, cleavage of DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well as lysosomal damage. Consequently, cell death by apoptosis and secondary necrosis is activated. Thus, we describe the first class of half-sandwich iridium cyclometalated complexes active in PDT.This work was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (PID2021-127187OB-C21,PID2021-127187OB-C22), PID2019-105408GB-I00, Junta de Comunidades de Castilla-La Mancha-FEDER (JCCM) (grant SBPLY/19/180501/000260), Junta de Castilla y León (BU087G19), and UCLM-FEDER (grants 2019-GRIN-27183and 2019-GRIN-27209). C.G. acknowledges his fellowship toboth the European Social Fund and Plan Propio de I+D+I of UCLM (2022-PRED-20649). G.D. thanks the Junta de Comunidades de Castilla la Mancha and EU for financialsupport through the European Regional Development Fund (project SBPLY/19/180501/000191). J.C.L. and A.M. acknowledge the Portuguese Foundation for Science and Technology for funding through LAQV-REQUIMTE (UIDB/50006/2020 and UIDP/50006/2020). Dr. F. Javier Galbán, head of the group “Analytical Biosensors Group” of Zaragoza University is also acknowledged.Peer reviewedAmerican Chemical SocietyAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionJunta de Comunidades de Castilla-La ManchaJunta de Castilla y LeónFundação para a Ciência e a Tecnologia (Portugal)Universidad de Castilla La ManchaUniversidad de ZaragozaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/380948reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C21info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127187OB-C22info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105408GB-I00Gonzalo-Navarro, Carlos; Zafon, Elisenda; Organero, Juan Angel; Jalón, Félix A.; Lima, João Carlos; Espino, Gustavo; Rodríguez, Ana María; Santos, Lucía; Moro, Artur J.; Barrabés, Sílvia; Castro, Jessica; Camacho-Aguayo, Javier; Massaguer, Anna; Manzano, Blanca R.; Durá, Gema; 2024; Supporting Information: Ir(III) half-sandwich photosensitizers with a π-expansive ligand for efficient anticancer photodynamic therapy [Dataset]; American Chemical Society; https://doi.org/10.1021/acs.jmedchem.3c01276https://doi.org/10.1021/acs.jmedchem.3c01276Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3809482026-05-22T06:33:51Z |
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15,811543 |