title: Nonfunctionalized nanocrystals can exploit a cell's active transport machinery delivering them to specific nuclear and cytoplasmic compartments.
abstract: We use high content cell analysis, live cell fluorescent imaging, and transmission electron microscopy approaches combined with inhibitors of cellular transport and nuclear import to conduct a systematic study of the mechanism of interaction of nonfunctionalized quantum dots (QDs) with live human blood monocyte-derived primary macrophages and cell lines of phagocytic, epithelial, and endothelial nature. Live human macrophages are shown to be able to rapidly uptake and accumulate QDs in distinct cellular compartment specifically to QDs size and charge. We show that the smallest QDs specifically target histones in cell nuclei and nucleoli by a multistep process involving endocytosis, active cytoplasmic transport, and entering the nucleus via nuclear pore complexes. Treatment of the cells with an anti-microtubule agent nocodazole precludes QDs cytoplasmic transport whereas a nuclear import inhibitor thapsigargin blocks QD import into the nucleus. These results demonstrate that the nonfunctionalized QDs exploit the cell's active transport machineries for delivery to specific intranuclear destinations.
authors.affiliation: EA No. 3798 Détection et Approches Thérapeutiques Nanotechnologiques dans Mécanismes Biologiques de Défense, Université de Reims Champagne-Ardenne, 51100 Reims, France. igor.nabiev@univ-reims.fr
authors.forename: Igor
authors.initials: I
authors.lastname: Nabiev
authors.forename: Siobhan
authors.initials: S
authors.lastname: Mitchell
authors.forename: Anthony
authors.initials: A
authors.lastname: Davies
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Williams
authors.forename: Dermot
authors.initials: D
authors.lastname: Kelleher
authors.forename: Richard
authors.initials: R
authors.lastname: Moore
authors.forename: Yurii K
authors.initials: YK
authors.lastname: Gun'ko
authors.forename: Stephen
authors.initials: S
authors.lastname: Byrne
authors.forename: Yury P
authors.initials: YP
authors.lastname: Rakovich
authors.forename: John F
authors.initials: JF
authors.lastname: Donegan
authors.forename: Alyona
authors.initials: A
authors.lastname: Sukhanova
authors.forename: Jennifer
authors.initials: J
authors.lastname: Conroy
authors.forename: David
authors.initials: D
authors.lastname: Cottell
authors.forename: Nikolai
authors.initials: N
authors.lastname: Gaponik
authors.forename: Andrey
authors.initials: A
authors.lastname: Rogach
authors.forename: Yuri
authors.initials: Y
authors.lastname: Volkov
mesh_terms: D001693:Biological Transport, Active; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D010587:Phagocytosis; D019284:Thapsigargin / Q000737:chemistry
chemical_list: D019284:Thapsigargin