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 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.
Nabiev
Igor
I
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
Mitchell
Siobhan
S
Davies
Anthony
A
Williams
Yvonne
Y
Kelleher
Dermot
D
Moore
Richard
R
Gun'ko
Yurii K
YK
Byrne
Stephen
S
Rakovich
Yury P
YP
Donegan
John F
JF
Sukhanova
Alyona
A
Conroy
Jennifer
J
Cottell
David
D
Gaponik
Nikolai
N
Rogach
Andrey
A
Volkov
Yuri
Y
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
D019284:Thapsigargin