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

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• 作者：Igor Nabiev ; Siobhan Mitchell ; Anthony Davies ; Yvonne Williams ; Dermot Kelleher ; Richard Moore ; Yurii K. Gun'ko ; Stephen Byrne ; Yury P. Rakovich ; John F. Donegan ; Alyona Sukhanova ; Jennifer Conroy ; Da
• 刊名：Nano Letters
• 出版年：2007
• 出版时间：November 2007
• 年：2007
• 卷：7
• 期：11
• 页码：3452 - 3461
• 全文大小：2023K
• 年卷期：v.7,no.11(November 2007)
• ISSN：1530-6992

文摘

We use high content cell analysis, live cell fluorescent imaging, and transmission electron microscopy approaches combined with inhibitorsof 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. Livehuman macrophages are shown to be able to rapidly uptake and accumulate QDs in distinct cellular compartment specifically to QDs size andcharge. 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 agentnocodazole precludes QDs cytoplasmic transport whereas a nuclear import inhibitor thapsigargin blocks QD import into the nucleus. Theseresults demonstrate that the nonfunctionalized QDs exploit the cell's active transport machineries for delivery to specific intranuclear destinations.