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dc.contributor.author | Klemt, Insa | |
dc.contributor.author | Reshetnikov, Viktor | |
dc.contributor.author | Dutta, Subrata | |
dc.contributor.author | Bila, Galyna | |
dc.contributor.author | Bilyy, Rostyslav | |
dc.contributor.author | Cuartero, Itziar Cossío | |
dc.contributor.author | Hidalgo, Andres | |
dc.contributor.author | Wünsche, Adrian | |
dc.contributor.author | Böhm, Maximilian | |
dc.contributor.author | Wondrak, Marit | |
dc.contributor.author | Kunz-Schughart, Leoni A | |
dc.contributor.author | Tietze, Rainer | |
dc.contributor.author | Beierlein, Frank | |
dc.contributor.author | Imhof, Petra | |
dc.contributor.author | Gensberger-Reigl, Sabrina | |
dc.contributor.author | Pischetsrieder, Monika | |
dc.contributor.author | Körber, Marlies | |
dc.contributor.author | Jost, Tina | |
dc.contributor.author | Mokhir, Andriy | |
dc.date.accessioned | 2024-07-03T10:12:34Z | |
dc.date.available | 2024-07-03T10:12:34Z | |
dc.date.issued | 2024-04-24 | |
dc.identifier.citation | RSC Med Chem. 2024 Jan 31;15(4):1189-1197. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19933 | |
dc.description.abstract | Many known chemotherapeutic anticancer agents exhibit neutropenia as a dose-limiting side effect. In this paper we suggest a prodrug concept solving this problem for camptothecin (HO-cpt). The prodrug is programmed according to Boolean "AND" logic. In the absence of H2O2 (trigger T1), e.g. in the majority of normal cells, it exists as an inactive oligomer. In cancer cells and in primed neutrophils (high H2O2), the oligomer is disrupted forming intermediate (inactive) lipophilic cationic species. These are accumulated in mitochondria (Mit) of cancer cells, where they are activated by hydrolysis at mitochondrial pH 8 (trigger T2) with formation of camptothecin. In contrast, the intermediates remain stable in neutrophils lacking Mit and therefore a source of T2. In this paper we demonstrated a proof-of-concept. Our prodrug exhibits antitumor activity both in vitro and in vivo, but is not toxic to normal cell and neutrophils in contrast to known single trigger prodrugs and the parent drug HO-cpt. | es_ES |
dc.description.sponsorship | We thank German Research Council (DFG) (AM 1418/7-2) and European Commission (861878 – NeutroCure) for funding this study. The CNIC is supported by the MCIN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). The contribution of DFG to the mass spectrometry unit (timsTOF Pro) is highly appreciated (INST 90/950-1). The authors acknowledge the scientific support and HPC resources provided by the Erlangen National High Performance Computing Center (NHR@FAU) of the FriedrichAlexander-Universität Erlangen-Nürnberg (FAU). The hardware is funded by the DFG. Open access funding enabled and organized by Projekt DEAL. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Royal Society of Chemistry (RSC) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | A concept of dual-responsive prodrugs based on oligomerization-controlled reactivity of ester groups: an improvement of cancer cells versus neutrophils selectivity of camptothecin. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 38665843 | es_ES |
dc.format.volume | 15 | es_ES |
dc.format.number | 4 | es_ES |
dc.format.page | 1189 | es_ES |
dc.identifier.doi | 10.1039/d3md00609c | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Fundación ProCNIC | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2632-8682 | es_ES |
dc.relation.publisherversion | 10.1039/d3md00609c | es_ES |
dc.identifier.journal | RSC medicinal chemistry | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Imagen de la Inflamación Cardiovascular y la Respuesta Inmune | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |