Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment

Glioblastoma is the most malignant and frequently occurring type of brain tumors in adults. Its treatment has been greatly hampered by the difficulty to achieve effective therapeutic concentration in the tumor sites due to its location and the blood–brain barrier. Intranasal administration has emerg...

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Autores: Mao, Xiaoman, Wu, Shuang, Calero Pérez, Pilar, Candiota, Ana Paula, Alfonso Triguero, Paula, Bruna, Jordi, Yuste, Víctor J., Lorenzo, Julia, Novio, Fernando, Ruiz Molina, Daniel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/295441
Acceso en línea:http://hdl.handle.net/10261/295441
Access Level:acceso abierto
Palabra clave:Glioblastoma
Bioinspired
Pt(IV)
Prodrug
Catechol
Platinum drugs
Intranasal
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network_name_str España
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dc.title.none.fl_str_mv Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
title Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
spellingShingle Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
Mao, Xiaoman
Glioblastoma
Bioinspired
Pt(IV)
Prodrug
Catechol
Platinum drugs
Intranasal
title_short Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
title_full Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
title_fullStr Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
title_full_unstemmed Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
title_sort Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma Treatment
dc.creator.none.fl_str_mv Mao, Xiaoman
Wu, Shuang
Calero Pérez, Pilar
Candiota, Ana Paula
Alfonso Triguero, Paula
Bruna, Jordi
Yuste, Víctor J.
Lorenzo, Julia
Novio, Fernando
Ruiz Molina, Daniel
author Mao, Xiaoman
author_facet Mao, Xiaoman
Wu, Shuang
Calero Pérez, Pilar
Candiota, Ana Paula
Alfonso Triguero, Paula
Bruna, Jordi
Yuste, Víctor J.
Lorenzo, Julia
Novio, Fernando
Ruiz Molina, Daniel
author_role author
author2 Wu, Shuang
Calero Pérez, Pilar
Candiota, Ana Paula
Alfonso Triguero, Paula
Bruna, Jordi
Yuste, Víctor J.
Lorenzo, Julia
Novio, Fernando
Ruiz Molina, Daniel
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
European Commission
Generalitat de Catalunya
European Cooperation in Science and Technology
Centro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (España)
Instituto de Salud Carlos III
La Caixa
Universidad Autónoma de Barcelona
China Scholarship Council
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Glioblastoma
Bioinspired
Pt(IV)
Prodrug
Catechol
Platinum drugs
Intranasal
topic Glioblastoma
Bioinspired
Pt(IV)
Prodrug
Catechol
Platinum drugs
Intranasal
description Glioblastoma is the most malignant and frequently occurring type of brain tumors in adults. Its treatment has been greatly hampered by the difficulty to achieve effective therapeutic concentration in the tumor sites due to its location and the blood–brain barrier. Intranasal administration has emerged as an alternative for drug delivery into the brain though mucopenetration, and rapid mucociliary clearance still remains an issue to be solved before its implementation. To address these issues, based on the intriguing properties of proteins secreted by mussels, polyphenol and catechol functionalization has already been used to promote mucopenetration, intranasal delivery and transport across the blood–brain barrier. Thus, herein we report the synthesis and study of complex 1, a Pt(IV) prodrug functionalized with catecholic moieties. This complex considerably augmented solubility in contrast to cisplatin and showed a comparable cytotoxic effect on cisplatin in HeLa, 1Br3G and GL261 cells. Furthermore, preclinical in vivo therapy using the intranasal administration route suggested that it can reach the brain and inhibit the growth of orthotopic GL261 glioblastoma. These results open new opportunities for catechol-bearing anticancer prodrugs in the treatment for brain tumors via intranasal administration.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
2023
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/10261/295441
url http://hdl.handle.net/10261/295441
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098027-B-C22
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113058GB-I00
info:eu-repo/grantAgreement/AEI//RED2018-102471-T
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http://dx.doi.org/10.3390/cancers14020410
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dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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 Synthesis and Validation of a Bioinspired Catechol-Functionalized Pt(IV) Prodrug for Preclinical Intranasal Glioblastoma TreatmentMao, XiaomanWu, ShuangCalero Pérez, PilarCandiota, Ana PaulaAlfonso Triguero, PaulaBruna, JordiYuste, Víctor J.Lorenzo, JuliaNovio, FernandoRuiz Molina, DanielGlioblastomaBioinspiredPt(IV)ProdrugCatecholPlatinum drugsIntranasalGlioblastoma is the most malignant and frequently occurring type of brain tumors in adults. Its treatment has been greatly hampered by the difficulty to achieve effective therapeutic concentration in the tumor sites due to its location and the blood–brain barrier. Intranasal administration has emerged as an alternative for drug delivery into the brain though mucopenetration, and rapid mucociliary clearance still remains an issue to be solved before its implementation. To address these issues, based on the intriguing properties of proteins secreted by mussels, polyphenol and catechol functionalization has already been used to promote mucopenetration, intranasal delivery and transport across the blood–brain barrier. Thus, herein we report the synthesis and study of complex 1, a Pt(IV) prodrug functionalized with catecholic moieties. This complex considerably augmented solubility in contrast to cisplatin and showed a comparable cytotoxic effect on cisplatin in HeLa, 1Br3G and GL261 cells. Furthermore, preclinical in vivo therapy using the intranasal administration route suggested that it can reach the brain and inhibit the growth of orthotopic GL261 glioblastoma. These results open new opportunities for catechol-bearing anticancer prodrugs in the treatment for brain tumors via intranasal administration.This work was supported by grant RTI2018-098027-B-C21, RTI2018-098027-B-C22 and PID2020-113058GB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF’s A way of making Europe as well as with the support from “Metalfármacos multifuncionales para el diagnóstico y la terapia” with grant RED2018-102471-T funded by MCIN/AEI/10.13039/501100011033. The ICN2 is funded by the CERCA programme/Generalitat de Catalunya. The ICN2 is supported by the Severo Ochoa Centres of Excellence programme, and grant SEV-2017-0706 is funded by MCIN/AEI/10.13039/501100011033. COST is kindly acknowledged for stimulating scientific discussion and financial support via the Cost Action CA 17140 “Cancer nanomedicine from the bench to the bedside”. A.P.C. received funding from the ATTRACT project funded by the EC under grant agreement 777222. The work was also supported by Centro de Investigación Biomédica en Red-Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN [http://www.ciber-bbn.es/en, accessed on 24 November 2021], CB06/01/0010), an initiative of the Instituto de Salud Carlos III (Spain). The PhD program of X.M. was supported by the La Caixa-Severo Ochoa International PhD Fellowship. We acknowledge the UAB predoctoral training program (14th Convocatoria PIF-19612, predoctoral fellowships for P.C.-P) and China Scholarship Council (predoctoral fellowship 201606990027 for S.W.).Multidisciplinary Digital Publishing InstituteMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)European CommissionGeneralitat de CatalunyaEuropean Cooperation in Science and TechnologyCentro de Investigación Biomédica en Red Bioingeniería, Biomateriales y Nanomedicina (España)Instituto de Salud Carlos IIILa CaixaUniversidad Autónoma de BarcelonaChina Scholarship CouncilConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320222023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/295441reponame: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##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098027-B-C21info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098027-B-C22info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113058GB-I00info:eu-repo/grantAgreement/AEI//RED2018-102471-Tinfo:eu-repo/grantAgreement/AEI//SEV-2017-0706info:eu-repo/grantAgreement/EC/H2020/777222http://dx.doi.org/10.3390/cancers14020410Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2954412026-05-22T06:33:51Z
score 15,81155

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