Nonfunctionalized Nanocrystals Can Exploit a Cell's Active Transport Machinery Delivering Them to Specific Nuclear and Cytoplasmic Compartments

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 bl...

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Bibliographic Details
Published in:Nano letters 2007-11, Vol.7 (11), p.3452-3461
Main Authors: Nabiev, Igor, Mitchell, Siobhan, Davies, Anthony, Williams, Yvonne, Kelleher, Dermot, Moore, Richard, Gun'ko, Yurii K, Byrne, Stephen, Rakovich, Yury P, Donegan, John F, Sukhanova, Alyona, Conroy, Jennifer, Cottell, David, Gaponik, Nikolai, Rogach, Andrey, Volkov, Yuri
Format: Article
Language:English
Subjects:
Applied sciences
Biological and medical sciences
Biological Transport, Active
Biotechnology
Cell Nucleus - metabolism
Cross-disciplinary physics: materials science
rheology
Cytoplasm - metabolism
Electronics
Endothelium - metabolism
Endothelium, Vascular - metabolism
Engineering Sciences
Epithelial Cells - metabolism
Exact sciences and technology
Fundamental and applied biological sciences. Psychology
Human health and pathology
Humans
Life Sciences
Macrophages - metabolism
Materials science
Methods. Procedures. Technologies
Micro and nanotechnologies
Microelectronics
Microscopy, Electron, Transmission
Models, Biological
Molecular electronics, nanoelectronics
Monocytes - metabolism
Nanocrystalline materials
Nanoparticles - chemistry
Nanoscale materials and structures: fabrication and characterization
Nanotechnology - methods
Others
Phagocytosis
Physics
Quantum dots
Semiconductor electronics. Microelectronics. Optoelectronics. Solid state devices
Thapsigargin - chemistry
Various methods and equipments
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Summary: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.
ISSN:1530-6984
1530-6992
DOI:10.1021/nl0719832