Cellular uptake and cytotoxicity of octahedral rhenium cluster complexes
Cellular uptake and cytotoxicity of octahedral rhenium cluster complexes
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DOI：
10.1016/j.jinorgbio.2008.07.013
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发表时间：
2008-11-01
影响因子：
3.9
通讯作者：
Choy, Jin-Ho
中科院分区：
文献类型：
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作者：
Choi, Soo Jin;Brylev, Konstantin A.;Choy, Jin-Ho
在人宫颈腺癌 HeLa 细胞中评估了一类新型八面体铼簇化合物六羟基配合物 K-4[{Re6S8}(OH)(6)] 中心点 8H(2)O (1) 和 K-4[{Re6Se8)(OH)(6)] 中心点 8H(2)O (2) 的细胞摄取行为。共聚焦显微镜和流式细胞术研究表明，铼簇 1 没有内化到细胞中，而铼簇 2 则内化到细胞中。聚合物与铼簇 1 的缀合，即衍生物 K-4[{Re6S8}(OH)(6)L] (3)（L 是两亲性二嵌段共聚物 MPEG550-CH2CONH-GlyPheLeuGlyPheLeu-COO-），以浓度依赖性方式显着增强细胞摄取，并且在孵育时间后主要定位于细胞质和细胞核中。铼簇 2 的摄取是通过能量依赖性内吞作用介导的，而铼簇 3 通过类似细胞融合的机制直接摄入细胞中。根据细胞毒性评价试验，在生物应用的实际浓度水平下，铼簇2和铼簇3在达到50μM时均未表现出急性细胞毒性作用。因此，预计铼簇配合物可以作为医疗诊断剂的有希望的潜在候选者。 (C) 2008 Elsevier Inc. 保留所有权利。
Cellular uptake behavior of a novel class of octahedral rhenium cluster compounds, hexahydroxo complexes K-4[{Re6S8}(OH)(6)] center dot 8H(2)O (1) and K-4[{Re6Se8)(OH)(6)] center dot 8H(2)O (2), was evaluated in human cervical adenocarcinoma HeLa cells. Confocal microscopy and flow cytometry studies demonstrated that rhenium cluster 1 was not internalized into cell, while rhenium cluster 2 was. Conjugation of a polymer to rhenium cluster 1, namely the derivative K-4[{Re6S8}(OH)(6)L] (3) (L is amphiphilic diblock copolymer MPEG550-CH2CONH-GlyPheLeuGlyPheLeu-COO-), considerably enhanced cellular uptake in a concentration-dependent manner and was predominantly localized in the cytoplasm and nucleus upon incubation time. The uptake of rhenium cluster 2 was mediated by energy-dependent endocytosis, whereas rhenium cluster 3 was directly ingested into cells by cell-fusion-like mechanism. According to the cytotoxicity evaluation test, both rhenium clusters 2 and 3 did not exhibit acute cytotoxic effects up to 50 mu M, at the practical concentration level of biological applications. It is, therefore, expected that the rhenium cluster complexes can be promising potential candidates as diagnostic agents for medical treatment. (C) 2008 Elsevier Inc. All rights reserved.