G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage

14 pages, 6 figures, 1 table

Detalles Bibliográficos
Autores: Saczuk, Karolina, Cottini, Maria V., Dudek, Marta, Mazur, Leszek M., Sánchez, Dario Puchán, López-Pacios, Lucía, Kassem, Ahmad, Matczyszyn, Katarzyna, Nogueira, Juan J., Monnereau, Cyrille, Martínez-Fernández, Lara, Jamroskovic, Jan, Cabanetos, Clément, Deiana, Marco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/397071
Acceso en línea:http://hdl.handle.net/10261/397071
https://api.elsevier.com/content/abstract/scopus_id/105008959275
Access Level:acceso abierto
Palabra clave:http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
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dc.title.none.fl_str_mv G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage
title G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage
spellingShingle G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage
Saczuk, Karolina
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
title_short G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage
title_full G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage
title_fullStr G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage
title_full_unstemmed G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage
title_sort G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damage
dc.creator.none.fl_str_mv Saczuk, Karolina
Cottini, Maria V.
Dudek, Marta
Mazur, Leszek M.
Sánchez, Dario Puchán
López-Pacios, Lucía
Kassem, Ahmad
Matczyszyn, Katarzyna
Nogueira, Juan J.
Monnereau, Cyrille
Martínez-Fernández, Lara
Jamroskovic, Jan
Cabanetos, Clément
Deiana, Marco
author Saczuk, Karolina
author_facet Saczuk, Karolina
Cottini, Maria V.
Dudek, Marta
Mazur, Leszek M.
Sánchez, Dario Puchán
López-Pacios, Lucía
Kassem, Ahmad
Matczyszyn, Katarzyna
Nogueira, Juan J.
Monnereau, Cyrille
Martínez-Fernández, Lara
Jamroskovic, Jan
Cabanetos, Clément
Deiana, Marco
author_role author
author2 Cottini, Maria V.
Dudek, Marta
Mazur, Leszek M.
Sánchez, Dario Puchán
López-Pacios, Lucía
Kassem, Ahmad
Matczyszyn, Katarzyna
Nogueira, Juan J.
Monnereau, Cyrille
Martínez-Fernández, Lara
Jamroskovic, Jan
Cabanetos, Clément
Deiana, Marco
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv National Science Centre (Poland)
European Commission
Slovak Academy of Sciences
Ministerio de Ciencia, Innovación y Universidades (España)
Centro de Supercomputación de Galicia
Swedish Research Council
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
topic http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
description 14 pages, 6 figures, 1 table
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/397071
https://api.elsevier.com/content/abstract/scopus_id/105008959275
url http://hdl.handle.net/10261/397071
https://api.elsevier.com/content/abstract/scopus_id/105008959275
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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https://doi.org/10.1039/D5NH00237K
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Royal Society of Chemistry (UK)
publisher.none.fl_str_mv Royal Society of Chemistry (UK)
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling G-quadruplex-driven molecular disassembly and type I-to-type II photophysical conversion of a heavy-atom-free photosensitizer for site-specific oxidative damageSaczuk, KarolinaCottini, Maria V.Dudek, MartaMazur, Leszek M.Sánchez, Dario PuchánLópez-Pacios, LucíaKassem, AhmadMatczyszyn, KatarzynaNogueira, Juan J.Monnereau, CyrilleMartínez-Fernández, LaraJamroskovic, JanCabanetos, ClémentDeiana, Marcohttp://metadata.un.org/sdg/3Ensure healthy lives and promote well-being for all at all ages14 pages, 6 figures, 1 tableG-quadruplex (G4)-targeted photosensitizers (PSs) are advancing precision oncology by confining DNA damage to malignant cells while sparing healthy tissue. Yet, molecular-level studies on the mechanisms and dynamics of G4 structure damage under PSs light-activation are limited. Here, we introduce DBI-POE, an activatable, heavy-atom-free PS derived from the G4-specific sulfur-substituted dibenzothioxanthene imide (S-DBI) and modified with a hydrophilic, bio-compatible polyoxyethylene (POE) side chain. In aqueous solution, owing to its amphiphilic character, DBI-POE self-assembles into nanoaggregates that disassemble upon binding to G4 DNA. This disassembly switches its photophysical behavior "turning on" its fluorescence while enabling two-photon near-infrared (NIR) excitation. Moreover, while DBI-POE follows a type I pathway in the aggregated state, producing superoxide anion (O2˙-) and hydroxyl (OH˙) radicals, it shifts to a type II mechanism that predominantly generates singlet oxygen (1O2) upon G4 binding. The generated 1O2 selectively oxidizes guanine residues, triggering G4 unfolding, a mechanism validated through biophysical experiments, dot blot assay and molecular dynamics (MD) simulations. Furthermore, biochemical experiments at single-base resolution reveal that photoactivated DBI-POE induces site-specific oxidative lesions at G4 sites, stalling DNA polymerase, while non-G4 regions remain unaffected. This combination of supramolecular disassembly, photophysical pathway switching, and G4-selective oxidative damage underscores the high specificity of DBI-POE, opening new avenues for the design of next-generation G4-targeted PSs for photodynamic cancer therapies.M. Deiana would like to acknowledge financial support from project no. 2022/47/P/NZ5/01156, which is co-funded by the National Science Centre and the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 945339. Funding for J. Jamroskovic was provided by the IMPULZ program of the Slovak Academy of Sciences under the Agreement on the Provision of Funds No. IM-2022-62. L. Lopez-Pacios acknowledges the FPU22/02196 grant from the Spanish Ministry of Science, Innovation and Universities (MICINN). L. Martıiez-Fernández acknowledges the grant PID2023-151719NA-I00 funded by MICIU/AEI/ 10.13039/501100011033 and FEDER, UE. J. Nogueira thanks the Spanish Ministry of Science and Innovation for funding support through the project CNS2022-135720 (MCIN/AEI/10.13039/ 501100011033). This research project was made possible through the access granted by the Galician Supercomputing Center (CESGA) to its supercomputing infrastructure. The authors thank Dr Aeson Chang at Monash University (Australia) for carefully reading the manuscript and providing insightful comments. We acknowledge Protein Production Sweden (PPS) for providing facilities and experimental support. PPS is funded by the Swedish Research Council as a national research infrastructure. We thank the members of Dr. Barak’s laboratory (Slovak Academy of Sciences) for their help with the initial biochemical experiments. We also thank Dr. Barancik (Slovak Academy of Sciences) for providing access to the Typhoon scanner.Peer reviewedRoyal Society of Chemistry (UK)National Science Centre (Poland)European CommissionSlovak Academy of SciencesMinisterio de Ciencia, Innovación y Universidades (España)Centro de Supercomputación de GaliciaSwedish Research CouncilConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/397071https://api.elsevier.com/content/abstract/scopus_id/105008959275reponame: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##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/H2020/945339info:eu-repo/grantAgreement/AEI//FPU22info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-151719NA-I00info:eu-repo/grantAgreement/AEI//CNS2022-135720https://doi.org/10.1039/D5NH00237KSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3970712026-05-22T06:33:51Z
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