Cellular trafficking of quantum dot-ligand bioconjugates and their induction of changes in normal routing of unconjugated ligands
Cellular trafficking of quantum dot-ligand bioconjugates and their induction of changes in normal routing of unconjugated ligands
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DOI：
10.1021/nl0803848
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发表时间：
2008-07-01
期刊：
影响因子：
10.8
通讯作者：
Iversen, Tore-Geir
中科院分区：
文献类型：
--
作者：
Tekle, Christina;van Deurs, Bo;Iversen, Tore-Geir
量子点（Qdots）能否作为相关的细胞内探针来研究配体在活细胞中的路由？通过共聚焦荧光显微镜研究了与植物毒素蓖麻毒素、滋贺毒素或配体转铁蛋白（Tf）偶联的量子点的细胞内运输。Tf：Qdots通过网格蛋白依赖的内吞作用被内化，但其再循环被阻断。与滋贺毒素不同，滋贺：Qdot生物缀合物不被路由至高尔基体。内化的蓖麻毒素：Qdot生物缀合物定位于与蓖麻毒素本身相同的内体，但在高尔基体中不可见。重要的是，我们发现蓖麻毒素的内体积累：Qdots影响蓖麻毒素和滋贺毒素的内体到高尔基体的转运：蓖麻毒素的转运减少，而滋贺毒素的转运增加。总之，数据揭示，尽管Qdot与配体的偶联不一定改变所研究的配体通常使用的内吞途径，但似乎配体偶联的Qdot纳米颗粒可以在内体内被阻止，并且以某种方式扰乱细胞中的正常内体分选。因此，结果表明量子点可能对细胞生理学具有严重后果。
Can quantum dots (Qdots) act as relevant intracellular probes to investigate routing of ligands in live cells? The intracellular trafficking of Qdots that were coupled to the plant toxin ricin, Shiga toxin, or the ligand transferrin (Tf) was studied by confocal fluorescence microscopy. The Tf:Qdots were internalized by clathrin-dependent endocytosis as fast as Tf, but their recycling was blocked. Unlike Shiga toxin, the Shiga:Qdot bioconjugate was not routed to the Golgi apparatus. The internalized ricin:Qdot bioconjugates localized to the same endosomes as ricin itself but could not be visualized in the Golgi apparatus. Importantly, we find that the endosomal accumulation of ricin:Qdots affects endosome-to-Golgi transport of both ricin and Shiga toxin: Transport of ricin was reduced whereas transport of Shiga toxin was increased. In conclusion, the data reveal that, although coupling of Qdots to a ligand does not necessarily change the endocytic pathway normally used by the ligands studied, it appears that the ligand-coupled Qdot nanoparticles can be arrested within endosomes and somehow perturb the normal endosomal sorting in cells. Thus, the results demonstrate that Qdots may have severe consequences on cell physiology.