Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry

Beyond their classical role as cytotoxics, Platinum (Pt) coordination complexes recently joined the selected group of transition metals capable of performing bioorthogonal reactions in living environments. To minimize their reactivity towards nucleophiles, which limit their catalytic performance, we...

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Autores: García-Peiro, José I., Ortega-Liébana, M. Carmen, Adam, Catherine, Lorente-Macías, Álvaro, Travnickova, Jana, Patton, E. Elizabeth, Guerrero-López, Paula, García-Aznar, José Manuel, Hueso, José L., Santamaría, Jesús, Unciti-Broceta, Asier
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:10261/389639
Acceso en línea:http://hdl.handle.net/10261/389639
Access Level:acceso abierto
Palabra clave:Anticancer drugs
Platinum
Bioorthogonal
Heterogeneous
Catalysis
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dc.title.none.fl_str_mv Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry
title Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry
spellingShingle Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry
García-Peiro, José I.
Anticancer drugs
Platinum
Bioorthogonal
Heterogeneous
Catalysis
title_short Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry
title_full Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry
title_fullStr Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry
title_full_unstemmed Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry
title_sort Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistry
dc.creator.none.fl_str_mv García-Peiro, José I.
Ortega-Liébana, M. Carmen
Adam, Catherine
Lorente-Macías, Álvaro
Travnickova, Jana
Patton, E. Elizabeth
Guerrero-López, Paula
García-Aznar, José Manuel
Hueso, José L.
Santamaría, Jesús
Unciti-Broceta, Asier
author García-Peiro, José I.
author_facet García-Peiro, José I.
Ortega-Liébana, M. Carmen
Adam, Catherine
Lorente-Macías, Álvaro
Travnickova, Jana
Patton, E. Elizabeth
Guerrero-López, Paula
García-Aznar, José Manuel
Hueso, José L.
Santamaría, Jesús
Unciti-Broceta, Asier
author_role author
author2 Ortega-Liébana, M. Carmen
Adam, Catherine
Lorente-Macías, Álvaro
Travnickova, Jana
Patton, E. Elizabeth
Guerrero-López, Paula
García-Aznar, José Manuel
Hueso, José L.
Santamaría, Jesús
Unciti-Broceta, Asier
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
European Research Council
Engineering and Physical Sciences Research Council (UK)
Melanoma Research Alliance (US)
Cancer Research UK
Junta de Andalucía
Gobierno de Aragón
Zebra Foundation
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Anticancer drugs
Platinum
Bioorthogonal
Heterogeneous
Catalysis
topic Anticancer drugs
Platinum
Bioorthogonal
Heterogeneous
Catalysis
description Beyond their classical role as cytotoxics, Platinum (Pt) coordination complexes recently joined the selected group of transition metals capable of performing bioorthogonal reactions in living environments. To minimize their reactivity towards nucleophiles, which limit their catalytic performance, we investigated the use of Pt(0) with different forms, sizes and surface functionalization. We report herein the development of PEGylated Pt nanodendrites with the capacity to activate prodyes and prodrugs in cell culture and in vivo. Their dendritic morphology together with their surface shielding through Pt-S-bonded PEGylation synergistically contributed to create catalytic nanoreactors compatible with the highly-crowded and reductive environment of the cell cytoplasm, thereby facilitating in situ bioorthogonal drug uncaging in cancer cells in 2D and 3D culture, including in microfluidic systems, and xenografted in zebrafish.
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
Publisher's version
info:eu-repo/semantics/publishedVersion
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status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/389639
url http://hdl.handle.net/10261/389639
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
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info:eu-repo/grantAgreement/EC/H2020/841990
info:eu-repo/grantAgreement/EC/H2020/742684
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2023-001286-S
The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1002/anie.202424037
https://doi.org/10.1002/anie.202424037

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dc.publisher.none.fl_str_mv Wiley-VCH
publisher.none.fl_str_mv Wiley-VCH
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 Dendritic platinum nanoparticles shielded by Pt-S PEGylation as intracellular reactors for bioorthogonal uncaging chemistryGarcía-Peiro, José I.Ortega-Liébana, M. CarmenAdam, CatherineLorente-Macías, ÁlvaroTravnickova, JanaPatton, E. ElizabethGuerrero-López, PaulaGarcía-Aznar, José ManuelHueso, José L.Santamaría, JesúsUnciti-Broceta, AsierAnticancer drugsPlatinumBioorthogonalHeterogeneousCatalysisBeyond their classical role as cytotoxics, Platinum (Pt) coordination complexes recently joined the selected group of transition metals capable of performing bioorthogonal reactions in living environments. To minimize their reactivity towards nucleophiles, which limit their catalytic performance, we investigated the use of Pt(0) with different forms, sizes and surface functionalization. We report herein the development of PEGylated Pt nanodendrites with the capacity to activate prodyes and prodrugs in cell culture and in vivo. Their dendritic morphology together with their surface shielding through Pt-S-bonded PEGylation synergistically contributed to create catalytic nanoreactors compatible with the highly-crowded and reductive environment of the cell cytoplasm, thereby facilitating in situ bioorthogonal drug uncaging in cancer cells in 2D and 3D culture, including in microfluidic systems, and xenografted in zebrafish.We are grateful to the EC (H2020-MSCA-IF-2018-841990) and EPSRC (EP/S010289/1) for financial support. We also would like to acknowledge the European Research Council (ERC) through the Catalytic Dual-Function Devices Against Cancer (CADENCE-742684) project, RLDI/2015-021. EEP is funded by the MRC (MC_UU_00035/13), Melanoma Research Alliance and Rosetrees Trust (MRA Awards 687306, 917226). This work was supported by the Cancer Research UK Scotland Centre (CTRQQR-2021\100006). MCOL is grateful to the Institute of Genetics and Cancer (IGC) for financial support through the Hastie Career Advancement Fund 2020, and the Consejeria de Universidad Investigacion e Innovacion by ERDF Andalusian Program 2021–2027 (A-EXP-278-UGR23). We thank IGC Zebrafish facility for supporting zebrafish management and IGC Imaging Facility for their support with imaging experiments. P.G.-L. gratefully acknowledges the support of the Government of Aragon (Grant No. 2021–25). The synthesis of materials has been performed by the Platform of Production of Biomaterials and Nanoparticles of the NANBIOSIS ICTS, more specifically by the Nanoparticle Synthesis Unit of the CIBER in BioEngineering, Biomaterials & Nanomedicine (CIBER-BBN). The TEM studies were conducted at the Laboratorio de Microscopias Avanzadas, Instituto de Nanociencia y Materiales de Aragon, Universidad de Zaragoza, Spain. (SAI and ELECMI). Ayuda CEX2023-001286-S financiada por MICIU/AEI/10.13039/501100011033.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2023-001286-S).Peer reviewedWiley-VCHEuropean CommissionEuropean Research CouncilEngineering and Physical Sciences Research Council (UK)Melanoma Research Alliance (US)Cancer Research UKJunta de AndalucíaGobierno de AragónZebra FoundationAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Instituto de Salud Carlos IIIConsejo 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/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/389639reponame: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/EC/H2020/841990info:eu-repo/grantAgreement/EC/H2020/742684info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2023-001286-SThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI 10.1002/anie.202424037https://doi.org/10.1002/anie.202424037Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3896392026-05-22T06:33:51Z
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