荧光显微镜直接观察氨氯地平干预活细胞的过程。

Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

Chromatin Imaging and Labeling Group, Department of NanoBiophotonics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

Molecules. 2021 May 18;26(10):2997. doi: 10.3390/molecules26102997.

Amlodipine, a unique long-lasting calcium channel antagonist and antihypertensive drug, has weak fluorescence in aqueous solutions. In the current paper, we show that direct visualization of amlodipine in live cells is possible due to the enhanced emission in cellular environment. We examined the impact of pH, polarity and viscosity of the environment as well as protein binding on the spectral properties of amlodipine in vitro, and used quantum chemical calculations for assessing the mechanism of fluorescence quenching in aqueous solutions. The confocal fluorescence microscopy shows that the drug readily penetrates the plasma membrane and accumulates in the intracellular vesicles. Visible emission and photostability of amlodipine allow confocal time-lapse imaging and the drug uptake monitoring.

氨氯地平是一种独特的长效钙通道拮抗剂和抗高血压药物，在水溶液中荧光很弱。在目前的论文中，我们表明，由于在细胞环境中增强了发射，因此可以直接在活细胞中可视化氨氯地平。我们研究了 pH 值、环境极性和粘度以及蛋白质结合对氨氯地平体外光谱性质的影响，并使用量子化学计算评估了水溶液中荧光猝灭的机制。共聚焦荧光显微镜表明，该药物容易穿透质膜并在细胞内囊泡中积累。氨氯地平的可见发射和光稳定性允许进行共聚焦延时成像和药物摄取监测。