In vivo stability and photodynamic efficacy of fluorinated bacteriopurpurinimides derived from bacteriochlorophyll-a
In vivo stability and photodynamic efficacy of fluorinated bacteriopurpurinimides derived from bacteriochlorophyll-a
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DOI：
10.1021/jm050919z
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发表时间：
2006-03-23
影响因子：
7.3
通讯作者：
Pandey, RK
中科院分区：
文献类型：
--
作者：
Gryshuk, AL;Chen, YH;Pandey, RK
由3，5-二(三氟甲基)苯甲胺与细菌紫红素甲酯反应得到的不稳定席夫碱(803 nm，在CH2Cl2中，epsilon：50900)还原得到稳定的细菌紫酰亚胺(788 nm，在CH2Cl2中的epsilon：38600)，产生了良好的光敏效果。核磁共振氢谱、质谱学和高效液相色谱分析证实了新的细菌紫红酰亚胺及其代谢产物的结构。这种稳定的细菌紫杉酰亚胺在体内的初步光敏效果是作为不同药物剂量的函数在荷有辐射诱导的纤维肉瘤的OH小鼠中被测定的。当药物剂量为1.0 mU/kg，照射剂量为135 J/cm(75 mW/cm 2，注射后24 h)，照射波长为796 nm，照射30min后，肿瘤的长期治愈率为60%(90d时，3/5的小鼠无瘤)。稳定的细菌紫质亚胺与MitoTracker Green的共定位研究证实了一些线粒体的定位。光动力疗法(PDT)后不同时间点的CD31荧光排斥试验和组织学染色证实血管停滞。治疗参数(药物最大摄取时间和光照波长)由体内反射光谱确定。
The stable bacteriopurpurinimide (788 nm, epsilon: 38 600 in CH2Cl2), obtained by reducing the corresponding unstable Schiff base (803 nm, epsilon: 50 900 in CH2Cl2) that was isolated by reacting bacteriopurpurin methyl ester with 3,5-bis-(trifluoromethyl)benzylamine, produced promising photosensitizing efficacy. H-1 NMR, mass spectrometry, and HPLC analyses confirmed the structures of new bacteriopurpurinimides and the metabolic product. The preliminary in vivo photosensitizing efficacy of this stable bacteriopurpurinimide was determined in OH mice bearing radiation induced fibrosarcoma tumors as a function of variable drug doses. A drug dose of 1.0 mu mol/kg and light exposure of 135 J/cm(2) (75 mW/cm(2); 24 h postinjection) at 796 nm for 30 min produced a 60% long-term tumor cure (3/5 mice were tumor-free on day 90). Colocalization study of the stable bacteriopurpurinimide with MitoTracker Green confirmed some mitochondrial localization. The fluorescein-exclusion assay and histological staining of CD31 confirmed vascular stasis at various time points post-PDT (post photodynamic therapy). The treatment parameters (time for maximum drug uptake and wavelength for light irradiation) were determined by in vivo reflectance spectroscopy.