Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2017-10-21 , DOI: 10.1016/j.bmc.2017.10.031 Jin Matsumoto , Kou Suzuki , Masahide Yasuda , Yuya Yamaguchi , Yoshitaka Hishikawa , Naoya Imamura , Atsushi Nanashima
A series of phosphorus porphyrin complexes ([(RO)2P(tpp)]Cl, tpp = tetraphenylporphyrinato group, R = −(CH2CH2O)m(CH2)nH; 1a: m = 2, n = 2; 1b: m = 2, n = 4; 1c: m = 2, n = 6; 1d: m = 3, n = 6) were used for the photodynamic therapy (PDT) of human biliary cancer cell line (NOZ) when exposed to the irradiation of light emitting diodes (LEDs). A Dulbecco’s modified Eagle’s medium (DMEM) containing NOZ cells (2000 cell well−1) and 1 (0–100 nM) was introduced into a 96-well microplate and incubated for 24 h to accumulate 1 into the NOZ cells and to multiply the NOZ cells until the cell number reached 104 cells well−1. After replacing the DMEM medium containing 1 with a fresh DMEM medium without 1, the plates were irradiated for 30 min at 610 nm. After incubation was performed for 24 h in dark conditions, the cell viability of the NOZ cells was determined using the MTT assay. The half maximum inhibitory concentrations 50 (IC50) of 1a–1d were found to be in the range of 33.7–58.7 nM for NOZ. These IC50 values for the NOZ were one hundredth the IC50 value (7.57 μM) for mono-l-aspartyl chlorin e6 (laserphyrin®). Thus, it was found that the PDT activity of 1a–1d was much higher than the mono-l-aspartyl chlorin e6. Similarly, IC50 vales of 1a–1d for HeLa cells were found to be 27.8–52.5 nM. This showed that 1a–1d had high photodynamic activity in cancer cells. At the same time, it was speculated that an LED is a useful light source for deactivating the cancer cells because it can excite the sensitizers with peak width in their absorption spectra using the light of the specified wave length with band width of 10–20 nm; LEDs provide a homogeneous light distribution for the target cells.
中文翻译:
磷卟啉和发光二极管的组合对人胆道癌细胞系的光动力治疗
一系列磷卟啉配合物([(RO)2 P(tpp)] Cl,tpp =四苯基卟啉基,R =-(CH 2 CH 2 O)m(CH 2)n H; 1a:m = 2,n = 2; 1b:m = 2,n = 4; 1c:m = 2,n = 6; 1d:m = 3,n 当暴露于发光二极管(LED)的照射时,= 6)被用于人胆道癌细胞系(NOZ)的光动力疗法(PDT)。将包含NOZ细胞(2000细胞孔-1)和1(0-100 nM)的Dulbecco改良的Eagle培养基(DMEM)引入96孔微孔板中,孵育24小时以将1累积到NOZ细胞中并繁殖。直到细胞数达到10 4个 细胞-1为止的NOZ细胞。替换含有DMEM培养基后1用新鲜的DMEM培养基而不1然后,将板在610nm下照射30分钟。在黑暗条件下孵育24小时后,使用MTT分析法确定NOZ细胞的细胞活力。发现1a – 1d的半数最大抑制浓度50(IC 50)在NOZ的33.7–58.7 nM范围内。NOZ的这些IC 50值是单-1-天冬氨酰二氢卟酚e6(laserphyrin®)的IC 50值(7.57μM)的百分之一百。因此,发现1a - 1d的PDT活性比单-1-天冬氨酰二氢卟酚e6高得多。同样,IC 50价位为1a –发现HeLa细胞的1d为27.8-52.5 nM。这表明1a – 1d在癌细胞中具有较高的光动力活性。同时,据推测,LED是使癌细胞失活的有用光源,因为它可以使用10-20 nm带宽的指定波长的光来激发其吸收光谱中具有峰值宽度的敏化剂。 ; LED为靶细胞提供均匀的光分布。