首页> 外文期刊>Photodiagnosis and Photodynamic Therapy >Photophysical properties and in vitro photocytotoxicity of disodium salt 2.4-di(alpha-methoxyethyl)-deuteroporphyrin-IX (Dimegine)
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Photophysical properties and in vitro photocytotoxicity of disodium salt 2.4-di(alpha-methoxyethyl)-deuteroporphyrin-IX (Dimegine)

机译:二钠盐2.4-二(α-甲氧基乙基)-氘卟啉-IX(地美辛)的光物理性质和体外光细胞毒性

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摘要

Photophysical and in vitro photocytotoxicity studies were performed for the photosensitizer Dimegine, a disodium salt 2.4-di(alpha-methoxyethyl)-deuteroporphyrin-IX with very low systemic toxicity. The singlet oxygen and luminescence quantum yield were Phi(Delta) = 0,65 +/- 0,06, and Phi(f) =0,11 +/- 0,01 respectively, and were independent of the excitation wavelength. The photobleaching coefficients for Dimegine dissolved in phosphate buffer (pH 7.4), and DMEM medium at concentration 2 mu M/l and in phosphate buffer (pH 7.0) at concentration 10 mu M/l were 16.10(-5), 9.10(-5) and 2.10(-5) respectively. In vitro cellular distribution and photocytotoxicity was studied in two human (U87 - primary glioblastoma and HT1376 - bladder cancer) and two rat cell lines (RG2 - glioma, and AY27 - bladder carcinoma). Fluorescence microscopy analysis shows primary Dimegine accumulation as small fluorescent inclusion bodies around the nuclei, suggesting an apoptotic over a necrotic cell death mechanism. The PDT efficacy was slightly higher for the rat cell lines over the human-derived cell lines, with LD 50 values of 2,5 mu M/l, 2.8 mu M/l, 4.5 mu M/l, 2.8 mu M/l using 530 nm excitation wavelength for AY27, RG2, HT1376 and U87 respectively, and 1.8 mu M/l, 2 mu M/l, 5 mu MA, 2.4 mu M/l using 625 nm excitation wavelength for AY27, RG2, HT1376 and U87 respectively. Comparison to literature data showed that Dimegine demonstrated improved phototherapeutic characteristics comparing to PpIX-mediated PDT.
机译:对光敏剂Dimegine(一种具有极低全身毒性的二钠盐2.4-二(α-甲氧基乙基)-氘卟啉-IX)进行了光物理和体外光细胞毒性研究。单线态氧和发光量子产率分别为PhiΔ= 0.65 +/- 0.06和Phi(f)= 0.11 +/- 0.01,并且与激发波长无关。溶于浓度为2μM / l的磷酸盐缓冲液(pH 7.4)和DMEM培养基和浓度为10μM / l的磷酸盐缓冲液(pH 7.0)中的Dimegine的光漂白系数分别为16.10(-5),9.10(-5) )和2.10(-5)。在两个人(U87-原发性胶质母细胞瘤和HT1376-膀胱癌)和两个大鼠细胞系(RG2-神经胶质瘤和AY27-膀胱癌)中研究了体外细胞分布和光细胞毒性。荧光显微镜分析显示,主要的Dimegine积累为细胞核周围小的荧光包涵体,表明细胞凋亡超过了坏死细胞的死亡机制。与人类来源的细胞系相比,大鼠细胞系的PDT效力略高,LD 50值分别为2.5μM/ l,2.8μM/ l,4.5μM/ l,2.8μM/ l,其中AY27,RG2,HT1376和U87的激发波长分别为530 nm和1.8μM/ l,2μM / l,5μMA,2.4μM/ l,而AY27,RG2,HT1376和U87的激发波长分别为625 nm 。与文献数据的比较表明,与PpIX介导的PDT相比,Dimegine具有改善的光疗特性。

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