Probing the Drug Dynamics of Chemotherapeutics Using Metasurface-Enhanced Infrared Reflection Spectroscopy of Live Cells.
Probing the Drug Dynamics of Chemotherapeutics Using Metasurface-Enhanced Infrared Reflection Spectroscopy of Live Cells.
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红外光谱学在生物应用方面已经引起了相当大的兴趣，但红外光在水中的衰减阻碍了对活细胞的测量。金属表面增强红外反射光谱(MeIRS)可以缓解这一问题，通过表面增强红外吸收来增强细胞的红外信号，同时将细胞的振动特征编码在反射光谱中。在这项研究中，我们使用MeIRS来研究活体癌细胞对一种新开发的具有不同作用模式的化疗金属络合物(MOAS)的动态反应：三羰基铼异腈多吡啶(TRIP)。MEIRS测量表明，服用TRIP可导致长期(数小时)蛋白质、脂肪和总折射率信号的减少，以及短期(数十分钟)这些信号的增加，这与内质网应激的诱导一致。在生物正交光谱窗口中实时监测TRIP的独特的三羰基红外特征，并将其用作红外标签来检测与表型反应的开始密切相关的精确给药时间。这些结果表明，MeIRS是一种有效的无标记实时细胞检测方法，能够检测和解释细胞对IR标记的化疗药物的早期表型反应。
Infrared spectroscopy has drawn considerable interest in biological applications, but the measurement of live cells is impeded by the attenuation of infrared light in water. Metasurface-enhanced infrared reflection spectroscopy (MEIRS) had been shown to mitigate the problem, enhance the cellular infrared signal through surface-enhanced infrared absorption, and encode the cellular vibrational signatures in the reflectance spectrum at the same time. In this study, we used MEIRS to study the dynamic response of live cancer cells to a newly developed chemotherapeutic metal complex with distinct modes of action (MoAs): tricarbonyl rhenium isonitrile polypyridyl (TRIP). MEIRS measurements demonstrated that administering TRIP resulted in long-term (several hours) reduction in protein, lipid, and overall refractive index signals, and in short-term (tens of minutes) increase in these signals, consistent with the induction of endoplasmic reticulum stress. The unique tricarbonyl IR signature of TRIP in the bioorthogonal spectral window was monitored in real time, and was used as an infrared tag to detect the precise drug delivery time that was shown to be closely correlated with the onset of the phenotypic response. These results demonstrate that MEIRS is an effective label-free real-time cellular assay capable of detecting and interpreting the early phenotypic responses of cells to IR-tagged chemotherapeutics.
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影响因子：
3.4
作者：
Fang, Ye;Ferrie, Ann M.;Balakrishnan, Jitendra
通讯作者：
Balakrishnan, Jitendra
DOI：
10.1073/pnas.1719551115
发表时间：
2018-06-19
影响因子：
11.1
作者：
Mittal S;Yeh K;Leslie LS;Kenkel S;Kajdacsy-Balla A;Bhargava R
通讯作者：
Bhargava R
DOI：
10.1016/j.bbamcr.2015.07.018
发表时间：
2015-10-01
影响因子：
5.1
作者：
Fale, Pedro L.;Altharawi, Ali;Chan, K. L. Andrew
通讯作者：
Chan, K. L. Andrew
影响因子：
3.9
作者：
Deng, Huayun;Wang, Chaoming;Fang, Ye
通讯作者：
Fang, Ye
影响因子：
6.1
作者：
Lehmkuhl, Brynson;Noblitt, Scott D.;Henry, Charles S.
通讯作者：
Henry, Charles S.