Stable Synthetic Cationic Bacteriochlorins as Selective Antimicrobial Photosensitizers
Stable Synthetic Cationic Bacteriochlorins as Selective Antimicrobial Photosensitizers
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DOI：
10.1128/aac.00125-10
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发表时间：
2010-09-01
影响因子：
4.9
通讯作者：
Hamblin, Michael R.
中科院分区：
文献类型：
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作者：
Huang, Liyi;Huang, Ying-Ying;Hamblin, Michael R.
光动力灭活是一种快速发展的抗微生物处理，其采用无毒的光活化染料或光敏剂与无害的可见光组合以产生对细胞有毒的活性氧物质。四吡咯（e.例如，在一个实施例中，卟啉、二氢卟酚、菌绿素）是一类光敏剂，其表现出用作广谱抗微生物剂的有希望的特性。为了结合并有效地渗透到所有种类的微生物细胞中，四吡咯应具有含有（i）一个或多个阳离子电荷或（ii）碱性基团的结构。在这份报告中，我们研究了使用新的稳定的合成菌绿素，具有较强的吸收带在720至740 nm的范围内，这是在近红外光谱区域。四个菌绿素与2，4，或6季铵基团或2个碱性胺基团进行了比较，光介导的杀伤革兰氏阳性细菌（金黄色葡萄球菌），革兰氏阴性细菌（大肠杆菌），和双态真菌酵母（白色念珠菌）。通过在相同条件下测定对人HeLa癌细胞的光毒性来评估选择性。所有四种化合物对S都具有高活性（在1 μ M或更低时杀死6个对数）。金黄色葡萄球菌，并显示出对细菌的选择性超过人类细胞。增加阳离子电荷可增加对大肠杆菌的活性。杆菌只有含碱性基团的化合物对C.白色念珠菌。支持的光化学和理论表征研究表明，（i）四种菌绿素在均匀溶液中具有可比的生物物理特性，（ii）预期的氧化还原特性与细胞杀伤能力无关。这些结果支持了这样的解释，即观察到的不同的生物活性源于细胞结合和定位效应，而不是内在的电子特性。这些研究结果进一步确立了阳离子菌绿素作为极具活性和选择性的近红外激活抗菌光敏剂，并且这些结果提供了抗菌光敏剂的构效关系的基本信息。
Photodynamic inactivation is a rapidly developing antimicrobial treatment that employs a nontoxic photo-activatable dye or photosensitizer in combination with harmless visible light to generate reactive oxygen species that are toxic to cells. Tetrapyrroles (e. g., porphyrins, chlorins, bacteriochlorins) are a class of photosensitizers that exhibit promising characteristics to serve as broad-spectrum antimicrobials. In order to bind to and efficiently penetrate into all classes of microbial cells, tetrapyrroles should have structures that contain (i) one or more cationic charge(s) or (ii) a basic group. In this report, we investigate the use of new stable synthetic bacteriochlorins that have a strong absorption band in the range 720 to 740 nm, which is in the near-infrared spectral region. Four bacteriochlorins with 2, 4, or 6 quaternized ammonium groups or 2 basic amine groups were compared for light-mediated killing against a Gram-positive bacterium (Staphylococcus aureus), a Gram-negative bacterium (Escherichia coli), and a dimorphic fungal yeast (Candida albicans). Selectivity was assessed by determining phototoxicity against human HeLa cancer cells under the same conditions. All four compounds were highly active (6 logs of killing at 1 mu M or less) against S. aureus and showed selectivity for bacteria over human cells. Increasing the cationic charge increased activity against E. coli. Only the compound with basic groups was highly active against C. albicans. Supporting photochemical and theoretical characterization studies indicate that (i) the four bacteriochlorins have comparable photophysical features in homogeneous solution and (ii) the anticipated redox characteristics do not correlate with cell-killing ability. These results support the interpretation that the disparate biological activities observed stem from cellular binding and localization effects rather than intrinsic electronic properties. These findings further establish cationic bacteriochlorins as extremely active and selective near-infrared activated antimicrobial photosensitizers, and the results provide fundamental information on structure-activity relationships for antimicrobial photosensitizers.