Electron Paramagnetic Resonance Implemented with Multiple Harmonic Detections Successfully Maps Extracellular pH In Vivo.
Electron Paramagnetic Resonance Implemented with Multiple Harmonic Detections Successfully Maps Extracellular pH In Vivo.
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DOI：
10.1021/acs.analchem.2c03194
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发表时间：
2023-02-28
影响因子：
7.4
通讯作者：
Hirata, Hiroshi
中科院分区：
文献类型：
--
作者：
Nakaoka, Ririko;Kato, Kazuhiro;Yamamoto, Kumiko;Yasui, Hironobu;Matsumoto, Shingo;Kirilyuk, Igor A.;Khramtsov, Valery V.;Inanami, Osamu;Hirata, Hiroshi
细胞外酸化表明癌细胞的代谢转变，与组织缺氧一起，是肿瘤恶性的标志。因此，非侵入性的细胞外pH （pHe）制图对于研究人员了解肿瘤微环境和监测肿瘤对代谢靶向药物的反应至关重要。虽然电子顺磁共振（EPR）已经成功地用于绘制小鼠异种移植模型中的pHe，但这种方法不够灵敏，无法用适量的外源性ph敏感探针绘制pHe。在这里，我们展示了一种改进的EPR系统通过使用多重谐波检测（MHD）方法实现了两倍的灵敏度提高，并提高了小鼠异种移植模型中pHe定位的稳健性。我们的研究结果表明，用碳酸酐酶IX （CAIX）抑制剂U-104治疗人源性胰腺导管腺癌细胞的小鼠异种移植模型可以延缓肿瘤的生长，同时有进一步细胞外酸化的趋势。我们预计基于epr的pHe制图可以扩展到监测其他代谢靶向药物的反应。此外，pHe监测还可用于开发改进的针对代谢的癌症治疗方法。
Extracellular acidification indicates a metabolic shift in cancer cells and is, along with tissue hypoxia, a hallmark of tumor malignancy. Thus, non-invasive mapping of extracellular pH (pHe) is essential for researchers to understand the tumor microenvironment and to monitor tumor response to metabolism-targeting drugs. While electron paramagnetic resonance (EPR) has been successfully used to map pHe in mouse xenograft models, this method is not sensitive enough to map pHe with a moderate amount of exogenous pH-sensitive probes. Here, we show that a modified EPR system achieves twofold higher sensitivity by using the multiple harmonic detection (MHD) method and improves the robustness of pHe mapping in mouse xenograft models. Our results demonstrate that treatment of a mouse xenograft model of human-derived pancreatic ductal adenocarcinoma cells with the carbonic anhydrase IX (CAIX) inhibitor U-104 delays tumor growth with a concurrent tendency toward further extracellular acidification. We anticipate that EPR-based pHe mapping can be expanded to monitor the response of other metabolism-targeting drugs. Furthermore, pHe monitoring can also be used for the development of improved metabolism-targeting cancer treatments.
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影响因子：
3.3
作者：
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通讯作者：
Cárdenas-Rodríguez J
影响因子：
8.8
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影响因子：
3.3
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通讯作者：
Khramtsov, Valery V.
影响因子：
7.4
作者：
Samouilov, Alexandre;Efimoya, Olga V.;Bobko, Andrey A.;Sun, Ziqi;Petryakov, Sergey;Eubank, Timothy D.;Trofimov, Dmitrii G.;Kirilyuk, Igor A.;Grigor'ev, Igor A.;Takahashi, Wataru;Zweier, Jay L.;Khramtsov, Valery V.
通讯作者：
Khramtsov, Valery V.
影响因子：
7.4
作者：
Komarov DA;Ichikawa Y;Yamamoto K;Stewart NJ;Matsumoto S;Yasui H;Kirilyuk IA;Khramtsov VV;Inanami O;Hirata H
通讯作者：
Hirata H