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电化学逆转诱导的光动力学反应中的花菁染料——体外人乳腺癌细胞研究

Cyanines in photodynamic reaction assisted by reversible electroporation--in vitro study on human breast carcinoma cells.

机构信息

Institute of Biomedical Engineering and Instrumentation, Wroclaw University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.

出版信息

Photodiagnosis Photodyn Ther. 2013 Dec;10(4):490-502. doi: 10.1016/j.pdpdt.2013.04.004. Epub 2013 Jun 16.

Abstract

BACKGROUND

Ineffective drug delivery is a vast problem of anticancer therapies. The aim of this study was to investigate the possibility of enhancement of cyanines transport through the cell membrane by electroporation and to evaluate a photodynamic activity of these compounds.

METHODS

We evaluated in vitro the effectiveness of photodynamic reaction with cyanines on breast adenocarcinoma cells (MCF-7/WT) and normal Chinese hamster ovary cells (CHO) lacking voltage-dependent ion channels, alone and combined with electropermeabilization. Among six cyanines tested, two compounds could be indicated as good therapeutic candidates: IR-775 and IR-786. Cellular effects were assessed with MTT assay reporting cell mitochondrial activity and with SRB assay based on the measurement of cellular protein content. Cyanines localization was observed with confocal microscope.

RESULTS

Photodynamic reaction of MCF-7/WT cells with IR-775 and IR-786 did not result in cellular dysfunction. Electric field intensities and pulse duration, non-toxic for cells, significantly increased photocytotoxicity of the cyanines after electropermeabilization with IR-775 and IR-786. Much shorter exposure times were efficient for cyanines in photodynamic reaction assisted by electroporation (10 min instead of 24h).

CONCLUSIONS

Our results indicate that electroporation of cancerous cells in the presence of cyanine dyes could increase the uptake of the photosensitizer, which correlates with a higher cytotoxicity in the breast adenocarcinoma cell line. Electroporation may be an attractive delivery system for photosensitizers in photodynamic therapy, enabling application of new compounds and reduction of drug dose and exposure time.

摘要

背景

无效的药物输送是癌症治疗中一个巨大的问题。本研究旨在探讨通过电穿孔增强菁染料跨细胞膜转运的可能性,并评估这些化合物的光动力活性。

方法

我们评估了体外光动力反应对 MCF-7/WT 乳腺癌细胞和缺乏电压依赖性离子通道的正常中国仓鼠卵巢细胞(CHO)的有效性,单独和与电穿孔联合使用。在测试的六种菁染料中,有两种化合物可以被认为是有前途的治疗候选物:IR-775 和 IR-786。用 MTT 测定法报告细胞线粒体活性,用 SRB 测定法基于细胞蛋白含量的测量来评估细胞毒性。用共聚焦显微镜观察菁染料的定位。

结果

IR-775 和 IR-786 与 MCF-7/WT 细胞的光动力反应不会导致细胞功能障碍。电场强度和脉冲持续时间(对细胞无毒)显著增加了电穿孔后 IR-775 和 IR-786 的光细胞毒性。在电穿孔辅助的光动力反应中,菁染料的曝光时间更短(10 分钟而不是 24 小时)就有效。

结论

我们的结果表明,在存在菁染料的情况下对癌细胞进行电穿孔可以增加光敏剂的摄取,这与乳腺癌细胞系中更高的细胞毒性相关。电穿孔可能是光动力疗法中光敏剂的一种有吸引力的输送系统,能够应用新的化合物,并减少药物剂量和暴露时间。

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