title: Probing cell-type-specific intracellular nanoscale barriers using size-tuned quantum dots.
abstract: The compartmentalization of size-tuned luminescent semiconductor nanocrystal quantum dots (QDs) in four distinctive cell lines, which would be representative of the most likely environmental exposure routes to nanoparticles in humans, is studied. The cells are fixed and permeabilized prior to the addition of the QDs, thus eliminating any cell-membrane-associated effects due to active QD uptake mechanisms or to specificity of signaling routes in different cell types, but leaving intact the putative physical subcellular barriers. All quantitative assays are performed using a high content analysis (HCA) platform, thereby obtaining robust data on large cell populations. While smaller QDs 2.1 nm in diameter enter the nuclei and localize to the nucleoli in all cell types, the rate and dynamics of their passage vary depending on the cell origin. As the QD size is increased to 4.4 nm, penetration into the cell is reduced but each cell line displays its own cutoff size thresholds reflecting cell-type-determined cytoplasmic and nuclear pore penetration specificity. These results give rise to important considerations regarding the differential compartmentalization and susceptibility of organs, tissues, and cells to nanoparticles, and may be of prime importance for biomedical imaging and drug-delivery research employing nanoparticle-based probes and systems.
authors.affiliation: Department of Clinical Medicine, Trinity College Dublin, Dublin 8, Ireland. williamy@tcd.ie
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Williams
authors.forename: Alyona
authors.initials: A
authors.lastname: Sukhanova
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Nowostawska
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Davies
authors.forename: Siobhan
authors.initials: S
authors.lastname: Mitchell
authors.forename: Vladimir
authors.initials: V
authors.lastname: Oleinikov
authors.forename: Yurii
authors.initials: Y
authors.lastname: Gun'ko
authors.forename: Igor
authors.initials: I
authors.lastname: Nabiev
authors.forename: Dermot
authors.initials: D
authors.lastname: Kelleher
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
mesh_terms: D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D008856:Microscopy, Fluorescence / Q000379:methods*; D015336:Molecular Probe Techniques; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D045663:Quantum Dots