Transferrin Serves As a Mediator to Deliver Organometallic Ruthenium(II) Anticancer Complexes into Cells
文献类型：期刊论文
| 作者 | Guo, Wei; Zheng, Wei; Luo, Qun; Li, Xianchan; Zhao, Yao; Xiong, Shaoxiang; Wang, Fuyi |
| 刊名 | INORGANIC CHEMISTRY
 |
| 出版日期 | 2013-05-06 |
| 卷号 | 52期号:9页码:5328-5338 |
| ISSN号 | 0020-1669 |
| DOI | 10.1021/ic4002626 |
| 英文摘要 | We report herein a systematic study on interactions of organometallic ruthenium(II) anticancer complex [(eta(6)-arene)Ru(en)Cl](+) (arene = p-cymene (1) or biphenyl (2), en = ethylenediamine) with human transferrin (hTf) and the effects of the hTf-ligation on the bioavailability of these complexes with cisplatin as a reference. Incubated with a 5-fold excess of complex 1, 2, or cisplatin, 1 mol of diferric hTf (holo-hTf) attached 0.62 mol of 1, 1.01 mol of 2, or 2.14 mol of cisplatin. Mass spectrometry revealed that both ruthenium complexes coordinated to N-donors His242, His273, His578, and His606, whereas cisplatin bound to 0 donors Tyr136 and Tyr317 and S-donor Met256 in addition to His273 and His578 on the surface of both apo- and holo-hTf. Moreover, cisplatin could bind to Thr457 within the C-lobe iron binding cleft of apo-hTf. Neither ruthenium nor platinum binding interfered with the recognition of holo-hTf by the transferrin receptor (TfR). The ruthenated/platinated holo-hTf complexes could be internalized via TfR-mediated endocytosis at a similar rate to that of holo-hTf itself. Moreover, the binding to holo-hTf well preserved the bioavailability of the ruthenium complexes, and the hTf-bound 1 and 2 showed a similar cytotoxicity toward the human breast cancer cell line MCF-7 to those of the complexes themselves. However, the conjugation with holo-hTf significantly reduced the cellular uptake of cisplatin and the amount of platinated DNA adducts formed intracellularly, leading to dramatic reduction of cisplatin cytotoxicity toward MCF-7. These findings suggest that hTf can serve as a mediator for the targeting delivery of Ru(arene) anticancer complexes while deactivating cisplatin. |
| 语种 | 英语 |
| WOS记录号 | WOS:000318669400070 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/54661]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Wang, Fuyi |
| 作者单位 | Chinese Acad Sci, Beijing Ctr Mass Spectrometry, CAS Key Lab Analyt Chem Living Biosyst, Beijing Natl Lab Mol Sci,Inst Chem, Beijing 100190, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Wei,Zheng, Wei,Luo, Qun,et al. Transferrin Serves As a Mediator to Deliver Organometallic Ruthenium(II) Anticancer Complexes into Cells[J]. INORGANIC CHEMISTRY,2013,52(9):5328-5338. |
| APA | Guo, Wei.,Zheng, Wei.,Luo, Qun.,Li, Xianchan.,Zhao, Yao.,...&Wang, Fuyi.(2013).Transferrin Serves As a Mediator to Deliver Organometallic Ruthenium(II) Anticancer Complexes into Cells.INORGANIC CHEMISTRY,52(9),5328-5338. |
| MLA | Guo, Wei,et al."Transferrin Serves As a Mediator to Deliver Organometallic Ruthenium(II) Anticancer Complexes into Cells".INORGANIC CHEMISTRY 52.9(2013):5328-5338. |
入库方式： OAI收割
来源：化学研究所
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