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A versatile drug delivery system targeting senescent cells

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dc.contributor.authorMuñoz Espin, Daniel
dc.contributor.authorRovira, Miguel
dc.contributor.authorGaliana, Irene
dc.contributor.authorGiménez, Cristina
dc.contributor.authorLozano-Torres, Beatriz
dc.contributor.authorPaez-Ribes, Marta
dc.contributor.authorLlanos, Susana
dc.contributor.authorChaib, Selim
dc.contributor.authorMuñoz-Martín, Maribel
dc.contributor.authorUcero, Alvaro C
dc.contributor.authorGaraulet, Guillermo
dc.contributor.authorMulero, Francisca
dc.contributor.authorDann, Stephen G
dc.contributor.authorVanArsdale, Todd
dc.contributor.authorShields, David J
dc.contributor.authorBernardos, Andrea
dc.contributor.authorMurguía, José Ramón
dc.contributor.authorMartínez-Máñez, Ramón
dc.contributor.authorSerrano Marugan , Manuel
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderMinisterio de Ciencia y Tecnología (España)
dc.contributor.funderBotín Foundation
dc.contributor.funderFundación La Caixa
dc.contributor.funderFundación Pfizer
dc.contributor.funderCambridge Centre Early Detection Programme  (CRUK)
dc.date.accessioned2018-11-02T12:18:58Z
dc.date.available2018-11-02T12:18:58Z
dc.date.issued2018-09
dc.description.abstractSenescent cells accumulate in multiple aging-associated diseases, and eliminating these cells has recently emerged as a promising therapeutic approach. Here, we take advantage of the high lysosomal β-galactosidase activity of senescent cells to design a drug delivery system based on the encapsulation of drugs with galacto-oligosaccharides. We show that gal-encapsulated fluorophores are preferentially released within senescent cells in mice. In a model of chemotherapy-induced senescence, gal-encapsulated cytotoxic drugs target senescent tumor cells and improve tumor xenograft regression in combination with palbociclib. Moreover, in a model of pulmonary fibrosis in mice, gal-encapsulated cytotoxics target senescent cells, reducing collagen deposition and restoring pulmonary function. Finally, gal-encapsulation reduces the toxic side effects of the cytotoxic drugs. Drug delivery into senescent cells opens new diagnostic and therapeutic applications for senescence-associated disorders.es_ES
dc.description.peerreviewedSí
dc.description.sponsorshipWe are grateful to D. Megías, L. Martínez, O. Domínguez, F. Al-Shahrour, C. Fustero, O. Graña, G. Gómez-López, A. De Martino, P. González, M. Udriste for technical support. Work in the laboratory of R.M.-M was funded by Project MAT2015-64139-C41-R, PROMETEOII/2014/047, and by Instituto de Salud Carlos III through the project “DTS16/00205”(Co-funded by European Regional Development Fund/European Social Fund“Investing in your future”). Work in the laboratory of M.S. was funded by the CNIO and the IRB, and by grants from the Spanish Ministry of Economy (MINECO, SAF), the European Research Council (ERC Advanced Grant), the Botin Foundation and Banco Santander (Santander Universities Global Division), and by la Caixa”Foundation. CNIO and IRB Barcelona are recipients of a Severo Ochoa Award of Excellence from the MINECO. D.M.-E was holder of a“Ramón y Cajal”Programme Senior Grant (MINECO, RYC-2013-14471) and was funded by a National Programme for Research Aimed at the Challenges of Society (MINECO, BFU 2014-60020-R).Work in the laboratory of D.M.-E. was funded by Cancer Research UK (CRUK, C9685/A25177), and by the CRUK Cambridge Centre Early Detection.Programme (RG 86786 ). M.R. was holder of a “ la Caixa ” -Severo Ochoa PhD scholarship. I.G., B.L.-T., and A.B. were funded by the Generalitat Valenciana and the MINECO. Part of this work has been funded by a research collabora- tion agreement between Pfizer Inc. and the laboratories of RM.-M. and M.S. The funders had no role in data collection and analysis, decision to publish, or preparation of the manuscript.es_ES
dc.format.number9es_ES
dc.format.pagee9355es_ES
dc.format.volume10es_ES
dc.identifier.citationEMBO Mol Med. 2018; 10 (9): pii: e9355.es_ES
dc.identifier.doi10.15252/emmm.201809355es_ES
dc.identifier.e-issn1757-4684es_ES
dc.identifier.issn1757-4676es_ES
dc.identifier.journalEMBO molecular medicinees_ES
dc.identifier.pubmedID30012580es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6559
dc.language.isoenges_ES
dc.publisherWiley
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2014-60020-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/MAT2015-64139-C4-1-Res_ES
dc.relation.publisherversionhttps://doi.org/10.15252/emmm.201809355es_ES
dc.repisalud.institucionCNIOes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectChemotherapyes_ES
dc.subjectFibrosises_ES
dc.subjectNanomedicinees_ES
dc.subjectPalbociclibes_ES
dc.subjectSenescencees_ES
dc.titleA versatile drug delivery system targeting senescent cellses_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
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