A general mechanism for intracellular toxicity of metal-containing nanoparticles

Handle URI:
http://hdl.handle.net/10754/334577
Title:
A general mechanism for intracellular toxicity of metal-containing nanoparticles
Authors:
Sabella, Stefania; Carney, Randy P.; Brunetti, Virgilio; Malvindi, Maria Ada; Al-Juffali, Noura; Vecchio, Giuseppe; Janes, Sam M.; Bakr, Osman M. ( 0000-0002-3428-1002 ) ; Cingolani, Roberto; Stellacci, Francesco; Pompa, Pier Paolo
Abstract:
The assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment-where particles are abundantly internalized-is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a "lysosome-enhanced Trojan horse effect" since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments. The Royal Society of Chemistry 2014.
KAUST Department:
Physical Sciences and Engineering (PSE) Division; Solar and Photovoltaic Engineering Research Center
Citation:
Sabella S, Carney RP, Brunetti V, Malvindi MA, Al-Juffali N, et al. (2014) A general mechanism for intracellular toxicity of metal-containing nanoparticles. Nanoscale 6: 7052. doi:10.1039/c4nr01234h.
Publisher:
Royal Society of Chemistry (RSC)
Journal:
Nanoscale
Issue Date:
9-Apr-2014
DOI:
10.1039/c4nr01234h
PubMed ID:
24842463
PubMed Central ID:
PMC4120234
Type:
Article
ISSN:
20403364
Appears in Collections:
Articles; Physical Sciences and Engineering (PSE) Division; Solar and Photovoltaic Engineering Research Center (SPERC)

Full metadata record

DC FieldValue Language
dc.contributor.authorSabella, Stefaniaen
dc.contributor.authorCarney, Randy P.en
dc.contributor.authorBrunetti, Virgilioen
dc.contributor.authorMalvindi, Maria Adaen
dc.contributor.authorAl-Juffali, Nouraen
dc.contributor.authorVecchio, Giuseppeen
dc.contributor.authorJanes, Sam M.en
dc.contributor.authorBakr, Osman M.en
dc.contributor.authorCingolani, Robertoen
dc.contributor.authorStellacci, Francescoen
dc.contributor.authorPompa, Pier Paoloen
dc.date.accessioned2014-11-11T14:30:28Z-
dc.date.available2014-11-11T14:30:28Z-
dc.date.issued2014-04-09en
dc.identifier.citationSabella S, Carney RP, Brunetti V, Malvindi MA, Al-Juffali N, et al. (2014) A general mechanism for intracellular toxicity of metal-containing nanoparticles. Nanoscale 6: 7052. doi:10.1039/c4nr01234h.en
dc.identifier.issn20403364en
dc.identifier.pmid24842463en
dc.identifier.doi10.1039/c4nr01234hen
dc.identifier.urihttp://hdl.handle.net/10754/334577en
dc.description.abstractThe assessment of the risks exerted by nanoparticles is a key challenge for academic, industrial, and regulatory communities worldwide. Experimental evidence points towards significant toxicity for a range of nanoparticles both in vitro and in vivo. Worldwide efforts aim at uncovering the underlying mechanisms for this toxicity. Here, we show that the intracellular ion release elicited by the acidic conditions of the lysosomal cellular compartment-where particles are abundantly internalized-is responsible for the cascading events associated with nanoparticles-induced intracellular toxicity. We call this mechanism a "lysosome-enhanced Trojan horse effect" since, in the case of nanoparticles, the protective cellular machinery designed to degrade foreign objects is actually responsible for their toxicity. To test our hypothesis, we compare the toxicity of similar gold particles whose main difference is in the internalization pathways. We show that particles known to pass directly through cell membranes become more toxic when modified so as to be mostly internalized by endocytosis. Furthermore, using experiments with chelating and lysosomotropic agents, we found that the toxicity mechanism for different metal containing NPs (such as metallic, metal oxide, and semiconductor NPs) is mainly associated with the release of the corresponding toxic ions. Finally, we show that particles unable to release toxic ions (such as stably coated NPs, or diamond and silica NPs) are not harmful to intracellular environments. The Royal Society of Chemistry 2014.en
dc.language.isoenen
dc.publisherRoyal Society of Chemistry (RSC)en
dc.rightshttp://creativecommons.org/licenses/by-nc/2.0/uk/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/2.0/uk/en
dc.subjectCell membranesen
dc.subjectCytologyen
dc.subjectIonsen
dc.subjectMachineryen
dc.subjectMolecular biologyen
dc.subjectRisk assessmenten
dc.subjectToxicityen
dc.subjectAcidic conditionsen
dc.subjectCascading eventsen
dc.subjectCellular machineryen
dc.subjectExperimental evidenceen
dc.subjectForeign objecten
dc.subjectGold particlesen
dc.subjectMetal-containing nanoparticlesen
dc.subjectToxicity mechanismsen
dc.subjectMetal nanoparticlesen
dc.titleA general mechanism for intracellular toxicity of metal-containing nanoparticlesen
dc.typeArticleen
dc.contributor.departmentPhysical Sciences and Engineering (PSE) Divisionen
dc.contributor.departmentSolar and Photovoltaic Engineering Research Centeren
dc.identifier.journalNanoscaleen
dc.identifier.pmcidPMC4120234en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionIstituto Italiano di Tecnologia, Center for Bio-Molecular Nanotechnologies at UniLe, Via Barsanti, 73010 Arnesano (Lecce), Italyen
dc.contributor.institutionInstitute of Materials, cole Polytechnique Fdrale de Lausanne (EPFL), CH-1015 Lausanne, Switzerlanden
dc.contributor.institutionCentre for Respiratory Research, Rayne Institute, University College London, 5 University Street, London WC1E 6JJ, United Kingdomen
dc.contributor.institutionIstituto Italiano di Tecnologia, Central Research Laboratories, Via Morego, 30-16136 Genova, Italyen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorBakr, Osman M.en
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