Correlative light-electron microscopy shows RGD-targeted ZnO nanoparticles dissolve in the intracellular environment of triple negative breast cancer cells and cause apoptosis with intra-tumor heterogeneity
File(s)
Accepted version
Author(s)
Type
Journal Article
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 extra-35 cellular effect, and the resistance among different cancer cell types to ZnO NP exposure. The present study quantified 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 appeared to increase the toxicity of the ZnO NPs to breast cancer cells at lower doses. Confocal microscopy of live MDA-MB-231 cells confirmed 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+ was 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 could be crucial for the development of optimized treatment strategies.
Date Issued
2016-04-25
Date Acceptance
2016-02-17
Citation
Advanced Healthcare Materials, 2016, 5 (11), pp.1310-1325
ISSN
2192-2640
Publisher
Wiley
Start Page
1310
End Page
1325
Journal / Book Title
Advanced Healthcare Materials
Volume
5
Issue
11
Copyright Statement
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the accepted version of the following article, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/adhm.201501012/abstract
Sponsor
Kaust UK Ltd
Commission of the European Communities
Grant Number
N/A
ERC-2010-StG-20091028
Subjects
cellular targeting
cytotoxicity
integrin αvβ3 receptors
triple negative breast cancer cells
zinc oxide nanoparticles
Publication Status
Published