pH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles

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dc.contributor.authorPlaza-GA, Ismael
dc.contributor.authorManzaneda González, Vanesa
dc.contributor.authorKisovec, Matic
dc.contributor.authorAlmendro Vedia, Víctor Galileo
dc.contributor.authorMuñoz Úbeda, Mónica
dc.contributor.authorAnderluh, Gregor
dc.contributor.authorGuerrero Martínez, Andrés
dc.contributor.authorNatale, Paolo
dc.contributor.authorLópez-Montero, Iván
dc.date.accessioned2023-06-17T12:30:01Z
dc.date.available2023-06-17T12:30:01Z
dc.date.issued2019
dc.descriptionThe research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (ERC grant agreement n° 338133)
dc.description.abstractBackground: A major bottleneck in drug delivery is the breakdown and degradation of the delivery system through the endosomal/lysosomal network of the host cell, hampering the correct delivery of the drug of interest. In nature, the bacterial pathogen Listeria monocytogenes has developed a strategy to secrete Listeriolysin O (LLO) toxin as a tool to escape the eukaryotic lysosomal system upon infection, allowing it to grow and proliferate unharmed inside the host cell. Results: As a “proof of concept”, we present here the use of purifed His-LLO H311A mutant protein and its conjuga tion on the surface of gold nanoparticles to promote the lysosomal escape of 40 nm-sized nanoparticles in mouse embryonic fbroblasts. Surface immobilization of LLO was achieved after specifc functionalization of the nanoparti cles with nitrile acetic acid, enabling the specifc binding of histidine-tagged proteins. Conclusions: Endosomal acidifcation leads to release of the LLO protein from the nanoparticle surface and its self-assembly into a 300 Å pore that perforates the endosomal/lysosomal membrane, enabling the escape of nanoparticles.
dc.description.departmentDepto. de Química Física
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.sponsorshipUnión Europea. FP7
dc.description.sponsorshipMinisterio de Ciencia e Innovación (MICINN)
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/60125
dc.identifier.doi10.1186/s12951-019-0543-6
dc.identifier.issn1477-3155
dc.identifier.officialurlhttps://doi.org/10.1186/s12951-019-0543-6
dc.identifier.urihttps://hdl.handle.net/20.500.14352/12302
dc.issue.number1
dc.journal.titleJournal of Nanobiotechnology
dc.language.isoeng
dc.publisherBMC
dc.relation.projectIDMITOCHON (338133)
dc.relation.projectID(RTI2018-095844-B-I00)
dc.relation.projectIDNANOBIOCARGO (S2018/NMT-4389)
dc.relation.projectID(PR75/18)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.keywordNanoparticles
dc.subject.keywordLysosomal escape
dc.subject.keywordListeriolysin O toxin
dc.subject.keywordQuantum dots
dc.subject.keywordDrug delivery
dc.subject.ucmFísica (Química)
dc.subject.ucmBiotecnología
dc.subject.unesco3399 Otras Especialidades Tecnológicas
dc.titlepH-triggered endosomal escape of pore-forming Listeriolysin O toxin-coated gold nanoparticles
dc.typejournal article
dc.volume.number17
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscovery1e5dbfe9-d8fa-4335-b08f-52bbc4855319
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