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Triphenylamines Induce Cell Death Upon 2-Photon Excitation

机译:三苯胺在2光子激发下诱导细胞死亡

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摘要

Photodynamic therapy (PDT) is a promising therapeutic method for several diseases, in particular for cancer. This approach uses a photosensitizer, oxygen, and an external light source to produce reactive oxygen species (ROS) at lethal doses to induce cell death. One drawback of current PDT is the use of visible light which has poor penetration in tissues. Such a limitation could be overcome by the use of novel organic compounds compatible with photoactivation under near-infrared light excitation. Triphenylamines (TPAs) are highly fluorescent compounds that are efficient to induce cell death upon visible light excitation (458 nm), but outside the biological spectral window. Interestingly, we recently showed that TPAs target cytoplasmic organelles of living cells, mainly mitochondria, and induce a high ROS production upon 2-photon excitation (in the 760-860 nm range), leading to a fast apoptosis process. However, we observed significant differences among the tested TPA compounds in terms of cell distribution and time courses of cell death–related events (apoptosis vs necrosis). In summary, TPAs represent serious candidates as photosensitizers that are compatible with 2-photon excitation to simultaneously trigger and imaging cell death although the relationship between their subcellular localization and the cell death mechanism involved is still a matter of debate.
机译:光动力疗法(PDT)是一种用于多种疾病,尤其是癌症的有前途的治疗方法。该方法使用光敏剂,氧气和外部光源以致命剂量产生活性氧(ROS),以诱导细胞死亡。当前PDT的一个缺点是使用可见光,该可见光在组织中的渗透性较差。通过使用与近红外光激发下的光活化相容的新型有机化合物可以克服这种限制。三苯胺(TPA)是高度荧光的化合物,可在可见光激发(458 nm)时有效地诱导细胞死亡,但在生物光谱窗口之外。有趣的是,我们最近显示,TPA靶向活细胞(主要是线粒体)的细胞质细胞器,并在2光子激发时(在760-860 nm范围内)诱导高ROS产生,从而导致快速的细胞凋亡过程。但是,我们观察到测试的TPA化合物之间在细胞分布和细胞死亡相关事件(凋亡与坏死)的时间过程方面存在显着差异。总而言之,TPA代表了作为与2光子激发同时触发和成像细胞死亡的光敏剂的严肃候选者,尽管它们的亚细胞定位与所涉及的细胞死亡机制之间的关系仍存在争议。

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