Correlative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity

Handle URI:
http://hdl.handle.net/10754/608631
Title:
Correlative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity
Authors:
Othman, Basmah A.; Greenwood, Christina; AbuElela, Ayman ( 0000-0002-4529-3156 ) ; Bharath, Anil A.; Chen, Shu; Theodorou, Ioannis; Douglas, Trevor; Uchida, Maskai; Ryan, Mary; Merzaban, Jasmeen S. ( 0000-0002-7276-2907 ) ; Porter, Alexandra E.
Abstract:
ZnO nanoparticles (NPs) are reported to show a high degree of cancer cell selectivity with potential use in cancer imaging and therapy. Questions remain about the mode by which the ZnO NPs cause cell death, whether they exert an intra- or extracellular effect, and the resistance among different cancer cell types to ZnO NP exposure. The present study quantifies the variability between the cellular toxicity, dynamics of cellular uptake, and dissolution of bare and RGD (Arg-Gly-Asp)-targeted ZnO NPs by MDA-MB-231 cells. Compared to bare ZnO NPs, RGD-targeting of the ZnO NPs to integrin αvβ3 receptors expressed on MDA-MB-231 cells appears to increase the toxicity of the ZnO NPs to breast cancer cells at lower doses. Confocal microscopy of live MDA-MB-231 cells confirms uptake of both classes of ZnO NPs with a commensurate rise in intracellular Zn2+ concentration prior to cell death. The response of the cells within the population to intracellular Zn2+ is highly heterogeneous. In addition, the results emphasize the utility of dynamic and quantitative imaging in understanding cell uptake and processing of targeted therapeutic ZnO NPs at the cellular level by heterogeneous cancer cell populations, which can be crucial for the development of optimized treatment strategies.
KAUST Department:
Cell Migration and Signaling Laboratory; Division of Biological and Environmental Sciences and Engineering
Citation:
Correlative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity 2016 Advanced Healthcare Materials
Publisher:
Wiley-Blackwell
Journal:
Advanced Healthcare Materials
Issue Date:
Apr-2016
DOI:
10.1002/adhm.201501012
Type:
Article
ISSN:
21922640
Additional Links:
http://doi.wiley.com/10.1002/adhm.201501012
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorOthman, Basmah A.en
dc.contributor.authorGreenwood, Christinaen
dc.contributor.authorAbuElela, Aymanen
dc.contributor.authorBharath, Anil A.en
dc.contributor.authorChen, Shuen
dc.contributor.authorTheodorou, Ioannisen
dc.contributor.authorDouglas, Trevoren
dc.contributor.authorUchida, Maskaien
dc.contributor.authorRyan, Maryen
dc.contributor.authorMerzaban, Jasmeen S.en
dc.contributor.authorPorter, Alexandra E.en
dc.date.accessioned2016-05-09T08:31:04Zen
dc.date.available2016-05-09T08:31:04Zen
dc.date.issued2016-04en
dc.identifier.citationCorrelative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity 2016 Advanced Healthcare Materialsen
dc.identifier.issn21922640en
dc.identifier.doi10.1002/adhm.201501012en
dc.identifier.urihttp://hdl.handle.net/10754/608631en
dc.description.abstractZnO nanoparticles (NPs) are reported to show a high degree of cancer cell selectivity with potential use in cancer imaging and therapy. Questions remain about the mode by which the ZnO NPs cause cell death, whether they exert an intra- or extracellular effect, and the resistance among different cancer cell types to ZnO NP exposure. The present study quantifies the variability between the cellular toxicity, dynamics of cellular uptake, and dissolution of bare and RGD (Arg-Gly-Asp)-targeted ZnO NPs by MDA-MB-231 cells. Compared to bare ZnO NPs, RGD-targeting of the ZnO NPs to integrin αvβ3 receptors expressed on MDA-MB-231 cells appears to increase the toxicity of the ZnO NPs to breast cancer cells at lower doses. Confocal microscopy of live MDA-MB-231 cells confirms uptake of both classes of ZnO NPs with a commensurate rise in intracellular Zn2+ concentration prior to cell death. The response of the cells within the population to intracellular Zn2+ is highly heterogeneous. In addition, the results emphasize the utility of dynamic and quantitative imaging in understanding cell uptake and processing of targeted therapeutic ZnO NPs at the cellular level by heterogeneous cancer cell populations, which can be crucial for the development of optimized treatment strategies.en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.relation.urlhttp://doi.wiley.com/10.1002/adhm.201501012en
dc.titleCorrelative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneityen
dc.typeArticleen
dc.contributor.departmentCell Migration and Signaling Laboratoryen
dc.contributor.departmentDivision of Biological and Environmental Sciences and Engineeringen
dc.identifier.journalAdvanced Healthcare Materialsen
dc.contributor.institutionDepartment of Materials; Imperial College London; Royal School of Mines; Exhibition Road London SW7 2AZ UKen
dc.contributor.institutionCell and Molecular Biology Research Laboratory; Faculty of Medical Sciences; Post Graduate Medical Institute; Anglia Ruskin University; Bishop Hall Lane; Chelmsford CM1 1SQ UKen
dc.contributor.institutionDepartment of Bioengineering; Imperial College London; Royal School of Mines; Exhibition Road London SW7 2AZ UKen
dc.contributor.institutionDepartment of Materials; Imperial College London; Royal School of Mines; Exhibition Road London SW7 2AZ UKen
dc.contributor.institutionDepartment of Materials; Imperial College London; Royal School of Mines; Exhibition Road London SW7 2AZ UKen
dc.contributor.institutionDepartment of Chemistry; Indiana University; 800 E. Kirkwood Avenue Bloomington IN 47405 USAen
dc.contributor.institutionDepartment of Chemistry; Indiana University; 800 E. Kirkwood Avenue Bloomington IN 47405 USAen
dc.contributor.institutionDepartment of Materials; Imperial College London; Royal School of Mines; Exhibition Road London SW7 2AZ UKen
dc.contributor.institutionDepartment of Materials; Imperial College London; Royal School of Mines; Exhibition Road London SW7 2AZ UKen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorAbuElela, Aymanen
kaust.authorMerzaban, Jasmeen S.en
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