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dc.contributor.authorQuarta, Alessandra
dc.contributor.authorAmorín López, Manuel
dc.contributor.authorAldegunde Rodríguez, María José
dc.contributor.authorBlasi, Laura
dc.contributor.authorRagusa, Andrea
dc.contributor.authorNitti, Simone
dc.contributor.authorPugliese, Giammarino
dc.contributor.authorGranja Guillán, Juan Ramón
dc.contributor.authorPellegrino, Teresa
dc.date.accessioned2020-04-13T20:18:51Z
dc.date.available2020-04-13T20:18:51Z
dc.date.issued2019
dc.identifier.citationQuarta, A., Amorín, M., Aldegunde, M., Blasi, L., Ragusa, A., & Nitti, S. et al. (2019). Novel synthesis of platinum complexes and their intracellular delivery to tumor cells by means of magnetic nanoparticles. Nanoscale, 11(48), 23482-23497. doi: 10.1039/c9nr07015j
dc.identifier.issn2040-3364
dc.identifier.urihttp://hdl.handle.net/10347/21331
dc.description.abstractPlatinum-based drugs are popular in clinics as chemotherapeutic agents to treat solid tumors. However, severe side effects such as nephro- and neurotoxicity impose strict dosage limitations that can lead to the development of drug resistance and tumor relapse. To overcome these issues Pt(IV) prodrugs and platinum delivery systems might represent the next generation of platinum-based drugs. In this study four novel Pt(II) complexes (namely, PEG-Glu-Pt-EDA, PEG-Glu-Pt-DACH, PEG-Mal-Pt-EDA and PEG-Mal-Pt-DACH) were synthesized and a general strategy to covalently bind them to iron oxide nanoparticles was developed. The intracellular uptake and cell distribution studies of Pt-tethered magnetic nanoparticles on breast and ovarian cancer cell line models indicate that binding of the Pt complexes to the nanoparticles facilitates, for all the complexes, cellular internalization. Moreover, the magnetic nanoparticles (MNPs), as shown in a magnetofection experiment, enhance the uptake of MNP-Pt conjugates if a magnet is placed beneath the culture dish of tumor cells. As shown by a Pt release experiment, intranuclear platinum quantification and TEM analysis on cell sections, the presence of a pH-sensitive dicarboxylic group coordinating the Pt complex, triggers platinum dissociation from the NP surface. In addition, the triazole moiety facilitates endosomal swelling and the leakage of platinum from the endosomes with intranuclear localization of platinum release by the NPs. Finally, as assessed by MTT, caspase, calcein/ethidium bromide live/dead assays, among the four NP-Pt conjugates, the NP-Glu-Pt-EDA complex having a glutamate ring and ethylenediamine as a chelating amine group of the platinum showed higher cytotoxicity than the other three MNP–platinum conjugates
dc.description.sponsorshipThis work was funded by the European Research Council (starting grant ICARO, Contract No. 678109) and partially supported by the European project Magnifyco (Contract No. NMP4-SL-2009-228622) and by the Project FISR—C.N.R. “Tecnopolo di Nanotecnologia e Fotonica per la Medicina di Precisione”— (CUPB83B17000010001). This work was also supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (CTQ2016-78423-R), and by the Xunta de Galicia and the ERDF (EM2014/011) and Centro singular de investigación de Galicia accreditation 2016–2019, (ED431G/09)
dc.language.isoeng
dc.publisherRoyal Society of Chemistry
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/678109
dc.relationinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2016-78423-R/ES
dc.rightsOpen Access Article. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence
dc.rights.urihttps://creativecommons.org/licenses/by-nc/3.0/
dc.subjectMagnetic nanoparticles
dc.subjectNanoparticles
dc.subjectTumor cells
dc.titleNovel synthesis of platinum complexes and their intracellular delivery to tumor cells by means of magnetic nanoparticles
dc.typeinfo:eu-repo/semantics/article
dc.identifier.DOI10.1039/c9nr07015j
dc.relation.publisherversionhttps://doi.org/10.1039/c9nr07015j
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.e-issn2040-3372
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.contributor.affiliationUniversidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Química Orgánica
dc.description.peerreviewedSI


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Open Access Article. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence
Except where otherwise noted, this item's license is described as  Open Access Article. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence





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