Monitoring drug induced changes in cardiomyocyte contractility with second harmonic generation (SHG) microscopy
Monitoring drug induced changes in cardiomyocyte contractility with second harmonic generation (SHG) microscopy
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使用二次谐波发生 (SHG) 显微镜监测药物引起的心肌细胞收缩力变化
DOI：
10.1117/12.2546825
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Chan, James W.
中科院分区：
文献类型：
--
作者：
Chang, Che-Wei;Kao, Hillary K.;Sun, Yao-Hui;Pretto, Dalyir I.;Lieu, Deborah K.;Chan, James W.
将一种药物推向市场的成本可能超过20亿美元。不断攀升的药物发现成本是在药物开发过程中尽早寻找新方法来预测新化合物的安全性和有效性的主要动机因素，以避免在临床试验后期阶段的药物磨损，甚至是批准的药物撤回。心脏毒性占美国上市后药物退出的近30%，一直是美国食品和药物管理局(FDA)关注的主要问题，美国食品和药物管理局(FDA)正专注于体外心脏毒性筛查，以将与药物相关的心脏风险降至最低。一种可以直接量化药物与心肌细胞之间相互作用而不受外源基因或化学标记干扰的技术将对直接筛选这些新药大有裨益。我们的研究小组此前已经证明，心肌细胞肌球蛋白细丝产生的二次谐波产生(SHG)信号可以作为一种强大的无标记光学技术，用于记录高空间和时间分辨率的细胞缩短动力学，这是因为心肌细胞中的肌球蛋白杆域能够发射倍频光。在不添加任何可能影响和改变细胞的自然细胞收缩能力的荧光标记的情况下记录动态。在这项研究中，我们使用倍频显微镜来测量药物引起的心肌细胞收缩能力的变化，并讨论其作为筛选药物和评估心脏毒性的工具的可行性。
The cost of taking a drug to market can exceed $2 billion dollars. The escalating cost of drug discovery is a major motivating factor for seeking new methods to predict the safety and efficacy of new compounds as early as possible in the drug development process to avoid drug attrition during late phases of clinical trials or even the withdrawal of approved drugs. Cardiotoxicity accounts for nearly 30% of US post-marketing drug withdrawal and remains a major concern to the point where the US Food and Drug Administration (FDA) is focused on in vitro cardiotoxicity screening to minimize cardiac risks associated with drugs. A technique that can directly quantify interactions between drugs and cardiomyocytes without the interference from exogenous genetic or chemical labels would be highly beneficial for directly screening these new drugs. Our group has previously shown that second harmonic generation (SHG) signals generated from myosin filaments in cardiomyocytes can be used as a robust label-free optical technique for recording cell shortening dynamics at high spatial and temporal resolution due to the ability of the myosin rod domains in heart muscle cells to emit the frequency-doubled light. The dynamics is recorded without adding any fluorescent labels that may otherwise affect and modify the natural cell contractility of the cell. In this study, we investigated the use of SHG microscopy for measuring drug-induced changes in cardiac cell contractility and discuss its feasibility as a tool for screening drugs and evaluating cardiotoxicity.
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DOI：
10.1016/s0021-9258(19)47321-3
发表时间：
1989-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Akwasi MintaS;Roger Y. TsienO
通讯作者：
Akwasi MintaS;Roger Y. TsienO
影响因子：
3
作者：
Meier, Silke D.;Kovalchuk, Yury;Rose, Christine R.
通讯作者：
Rose, Christine R.
通过 SHG 显微镜对单个微管进行无标记观察
DOI：
--
发表时间：
2014
期刊：
影响因子：
--
作者：
J. Kaneshiro;T. Shima;Y. Okada;T. Ichimura;Tomonobu M. Watanabe
通讯作者：
Tomonobu M. Watanabe
影响因子：
4
作者：
Lundy, Scott D.;Zhu, Wei-Zhong;Laflamme, Michael A.
通讯作者：
Laflamme, Michael A.
影响因子：
5.9
作者：
Kopljar, Ivan;Lu, Hua Rong;Gallacher, David J.
通讯作者：
Gallacher, David J.