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Cathepsin L Digestion of Nanobioconjugates upon Endocytosis

hal.structure.identifierCentre for Cell imaging
dc.contributor.authorSÉE, Violaine
hal.structure.identifierLiverpool Institute for Nanoscale Science and Technology [LINSET]
dc.contributor.authorFREE, Paul
hal.structure.identifierLiverpool Institute for Nanoscale Science and Technology [LINSET]
dc.contributor.authorCESBRON, Yann
hal.structure.identifierLiverpool Institute for Nanoscale Science and Technology [LINSET]
hal.structure.identifierPhysiological Laboratory
dc.contributor.authorNATIVO, Paula
hal.structure.identifierLiverpool Institute for Nanoscale Science and Technology [LINSET]
dc.contributor.authorSHAHEEN, Umbreen
hal.structure.identifierSchool of Biological Sciences
dc.contributor.authorRIGDEN, Daniel J.
hal.structure.identifierCentre for Cell imaging
dc.contributor.authorSPILLER, David G.
hal.structure.identifierLiverpool Institute for Nanoscale Science and Technology [LINSET]
dc.contributor.authorFERNIG, David G.
hal.structure.identifierCentre for Cell imaging
dc.contributor.authorWHITE, Michael R. H.
hal.structure.identifierPhysiological Laboratory
dc.contributor.authorPRIOR, Ian A.
hal.structure.identifierLiverpool Institute for Nanoscale Science and Technology [LINSET]
dc.contributor.authorBRUST, Mathias
hal.structure.identifierCentre de physique moléculaire optique et hertzienne [CPMOH]
dc.contributor.authorLOUNIS, Brahim
hal.structure.identifierLiverpool Institute for Nanoscale Science and Technology [LINSET]
dc.contributor.authorLEVY, Raphael
dc.date.created2009-06-29
dc.date.issued2009-09-22
dc.identifier.issn1936-0851
dc.description.abstractEnUnderstanding the dynamic fate and interactions of bioconjugated nanoparticles within living cells and organisms is a prerequisite for their use as in situ sensors or actuators. While recent research has provided indications on the effect of size, shape, and surface properties of nanoparticles on their internalization by living cells, the biochemical fate of the nanoparticles after internalization has been essentially unknown. Here we show that, upon internalization in a wide range of mammalian cells, biological molecules attached to the nanoparticles are degraded within the endosomal compartments through peptide cleavage by the protease cathepsin L. Importantly, using bioinformatics tools, we show that cathepsin L is able to cleave more than a third of the human proteome, indicating that this degradation process is likely to happen to most nanoparticles conjugated with peptides and proteins and cannot be ignored in the design of nanomaterials for intracellular applications. Preservation of the bioconjugates can be achieved by a combination of cathepsin inhibition and endosome disruption. Understanding the dynamic fate and interactions of bioconjugated nanoparticles within living cells and organisms is a prerequisite for their use as in situ sensors or actuators. While recent research has provided indications on the effect of size, shape, and surface properties of nanoparticles on their internalization by living cells, the biochemical fate of the nanoparticles after internalization has been essentially unknown. Here we show that, upon internalization in a wide range of mammalian cells, biological molecules attached to the nanoparticles are degraded within the endosomal compartments through peptide cleavage by the protease cathepsin L. Importantly, using bioinformatics tools, we show that cathepsin L is able to cleave more than a third of the human proteome, indicating that this degradation process is likely to happen to most nanoparticles conjugated with peptides and proteins and cannot be ignored in the design of nanomaterials for intracellular applications. Preservation of the bioconjugates can be achieved by a combination of cathepsin inhibition and endosome disruption.
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.subject.enpeptide
dc.subject.enself-assembled monolayer
dc.subject.enendocytosis
dc.subject.enbionanotechnology
dc.subject.ennanomedicine
dc.subject.engold nanoparticles
dc.subject.enprotease
dc.title.enCathepsin L Digestion of Nanobioconjugates upon Endocytosis
dc.typeArticle de revue
dc.identifier.doi10.1021/nn9006994
bordeaux.journalACS Nano
bordeaux.page2461-8
bordeaux.volume3
bordeaux.issue9
bordeaux.peerReviewedoui
hal.identifierhal-00670490
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-00670490v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=ACS%20Nano&rft.date=2009-09-22&rft.volume=3&rft.issue=9&rft.spage=2461-8&rft.epage=2461-8&rft.eissn=1936-0851&rft.issn=1936-0851&rft.au=S%C3%89E,%20Violaine&FREE,%20Paul&CESBRON,%20Yann&NATIVO,%20Paula&SHAHEEN,%20Umbreen&rft.genre=article


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