title: Quantification of ZnO nanoparticle uptake, distribution, and dissolution within individual human macrophages.
abstract: The usefulness of zinc oxide (ZnO) nanoparticles has led to their wide distribution in consumer products, despite only a limited understanding of how this nanomaterial behaves within biological systems. From a nanotoxicological viewpoint the interaction(s) of ZnO nanoparticles with cells of the immune system is of specific interest, as these nanostructures are readily phagocytosed. In this study, rapid scanning X-ray fluorescence microscopy was used to assay the number ZnO nanoparticles associated with ∼1000 individual THP-1 monocyte-derived human macrophages. These data showed that nanoparticle-treated cells endured a 400% elevation in total Zn levels, 13-fold greater than the increase observed when incubated in the presence of an equitoxic concentration of ZnCl2. Even after excluding the contribution of internalized nanoparticles, Zn levels in nanoparticle treated cells were raised ∼200% above basal levels. As dissolution of ZnO nanoparticles is critical to their cytotoxic response, we utilized a strategy combining ion beam milling, X-ray fluorescence and scanning electron microscopy to directly probe the distribution and composition of ZnO nanoparticles throughout the cellular interior. This study demonstrated that correlative photon and ion beam imaging techniques can provide both high-resolution and statistically powerful information on the biology of metal oxide nanoparticles at the single-cell level. Our approach promises ready application to broader studies of phenomena at the interface of nanotechnology and biology.
authors.affiliation: Australian Synchrotron , Clayton, Victoria 3168, Australia.
authors.forename: Simon A
authors.initials: SA
authors.lastname: James
authors.forename: Bryce N
authors.initials: BN
authors.lastname: Feltis
authors.forename: Martin D
authors.initials: MD
authors.lastname: de Jonge
authors.forename: Manoj
authors.initials: M
authors.lastname: Sridhar
authors.forename: Justin A
authors.initials: JA
authors.lastname: Kimpton
authors.forename: Matteo
authors.initials: M
authors.lastname: Altissimo
authors.forename: Sheridan
authors.initials: S
authors.lastname: Mayo
authors.forename: Changxi
authors.initials: C
authors.lastname: Zheng
authors.forename: Andrew
authors.initials: A
authors.lastname: Hastings
authors.forename: Daryl L
authors.initials: DL
authors.lastname: Howard
authors.forename: David J
authors.initials: DJ
authors.lastname: Paterson
authors.forename: Paul Frank A
authors.initials: PF
authors.lastname: Wright
authors.forename: Gareth F
authors.initials: GF
authors.lastname: Moorhead
authors.forename: Terence W
authors.initials: TW
authors.lastname: Turney
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
mesh_terms: D002460:Cell Line; D016000:Cluster Analysis; D003035:Cobalt / Q000737:chemistry; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D036103:Nanotechnology; D010587:Phagocytosis; D012995:Solubility; D013052:Spectrometry, X-Ray Emission; D015034:Zinc Oxide / Q000737:chemistry*
chemical_list: D003035:Cobalt; D015034:Zinc Oxide