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通过飞行时间二次离子质谱法评估细胞的内部分布和细胞外作用。

Evaluation of Internal Distribution and Extracellular Action of the Cell via TOF-SIMS.

作者信息

Tamura Kazuya, Hasegawa Takurou, Morita Masato, Sakamoto Tetsuo

机构信息

Graduate School of Electric Engineering and Electronics, Kogakuin University, 2665-1 Nakano-machi, Hachioji, Tokyo, 192-0015, Japan.

Department of Applied physics School of Advanced Engineering, Kogakuin University, 2665-1 Nakano-machi, Hachioji, Tokyo, 192-0015, Japan.

出版信息

Anal Sci. 2021 Apr 10;37(4):619-623. doi: 10.2116/analsci.20P149. Epub 2020 Oct 23.

DOI:10.2116/analsci.20P149
PMID:33100303
Abstract

Cisplatin is one of the most popular and traditional platinum-based anti-cancer drugs. Additionally, it is known for its effect on different types of cancers. To clarify the reaction mechanism of anti-cancer drugs in a cell, the visualization of drugs in a single cell is required. In this study, we investigated a secondary ion species obtained from cisplatin, which was bounded to the nucleus in a cell and its intensity. PtCl was mainly detected via SIMS during an analysis of pure cisplatin reagent. In contrast, a high-intensity signal for PtCN was detected from cultured cells that were administered cisplatin. However, this signal was not detected from cisplatin in the reagent state. Chlorine in the cisplatin structure is replaced with water when it is combined with the cell nucleus. Therefore, PtCN was mainly detected from the intracellular region because the structure was changed by cisplatin binding to the nucleus and which exhibits anti-cancer activity. The results showed that the cisplatin selectively combined with the nucleus. Through TOF-SIMS, we achieved a visual distribution of the cisplatin intracellular nucleus.

摘要

顺铂是最常用且传统的铂类抗癌药物之一。此外,它以对不同类型癌症的疗效而闻名。为阐明抗癌药物在细胞内的反应机制,需要对单个细胞内的药物进行可视化研究。在本研究中,我们研究了从顺铂中获得的二次离子种类,其在细胞内与细胞核结合及其强度。在对纯顺铂试剂进行分析时,主要通过二次离子质谱法检测到PtCl。相比之下,在给予顺铂的培养细胞中检测到了高强度的PtCN信号。然而,在试剂状态的顺铂中未检测到该信号。当顺铂结构中的氯与细胞核结合时,会被水取代。因此,主要从细胞内区域检测到PtCN,因为顺铂与细胞核结合导致结构发生变化,从而表现出抗癌活性。结果表明,顺铂选择性地与细胞核结合。通过飞行时间二次离子质谱法,我们实现了顺铂在细胞内核的可视化分布。

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本文引用的文献

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Challenges in biomarker discovery with MALDI-TOF MS.基质辅助激光解吸电离飞行时间质谱在生物标志物发现中的挑战。
Clin Chim Acta. 2016 Jul 1;458:84-98. doi: 10.1016/j.cca.2016.04.033. Epub 2016 Apr 28.
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Platinum-based drugs: past, present and future.铂类药物:过去、现在与未来。
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抗癌四唑桥联双核铂(II)配合物对顺铂耐药细胞的高效摄取及其与DNA配位结合后的异构化作用
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