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新型亲脂性卟啉衍生物的光谱性质和光动力效应:疗效、定位及细胞死亡途径

Spectroscopic properties and photodynamic effects of new lipophilic porphyrin derivatives: efficacy, localisation and cell death pathways.

作者信息

Kramer-Marek Gabriela, Serpa Carlos, Szurko Agnieszka, Widel Maria, Sochanik Aleksander, Snietura Miroslaw, Kus Piotr, Nunes Rui M D, Arnaut Luis G, Ratuszna Alicja

机构信息

A.Chelkowski Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice, Poland.

出版信息

J Photochem Photobiol B. 2006 Jul 3;84(1):1-14. doi: 10.1016/j.jphotobiol.2005.12.011. Epub 2006 Feb 21.

DOI:10.1016/j.jphotobiol.2005.12.011
PMID:16495073
Abstract

Photodynamic therapy (PDT) and photodynamic diagnostics (PDD) of cancer are based on the use of non-toxic dyes (photosensitisers) in combination with harmless visible light. This paper reports physicochemical properties, cell uptake, localisation as well as photodynamic efficiency of two novel lipophilic porphyrin derivatives, suitable for use as PDT sensitisers. Both compounds are characterised by high quantum yield of singlet oxygen generation which was measured by time-resolved phosphorescence. Photodynamic in vitro studies were conducted on three cancer cell lines. Results of cell survival tests showed negligible dark cytotoxicity but high phototoxicity. The results also indicate that cell death is dependent on energy dose and time following light exposure. Using confocal laser scanning microscopy both compounds were found to localise in the cytoplasm around the nucleus of the tumour cells. The mode of cell death was evaluated based on the morphological changes after differential staining. In summary, good photostability, high quantum yield of singlet oxygen and biological effectiveness indicate that the examined lipophilic porphyrin derivatives offer quite interesting prospects of photodynamic therapy application.

摘要

癌症的光动力疗法(PDT)和光动力诊断(PDD)基于使用无毒染料(光敏剂)并结合无害可见光。本文报道了两种新型亲脂性卟啉衍生物的物理化学性质、细胞摄取、定位以及光动力效率,它们适合用作光动力疗法的敏化剂。两种化合物的特征均为单线态氧生成的高量子产率,这是通过时间分辨磷光测量的。对三种癌细胞系进行了光动力体外研究。细胞存活测试结果显示暗细胞毒性可忽略不计,但光毒性高。结果还表明细胞死亡取决于能量剂量和光照后的时间。使用共聚焦激光扫描显微镜发现两种化合物均定位于肿瘤细胞核周围的细胞质中。基于差异染色后的形态变化评估细胞死亡模式。总之,良好的光稳定性、单线态氧的高量子产率和生物学有效性表明,所研究的亲脂性卟啉衍生物为光动力疗法的应用提供了相当有趣的前景。

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