Selective Photodynamic Inactivation of Bacterial Cells over Mammalian Cells by New Triarylmethanes
Selective Photodynamic Inactivation of Bacterial Cells over Mammalian Cells by New Triarylmethanes
复制标题
新型三芳基甲烷对细菌细胞相对于哺乳动物细胞的选择性光动力灭活
DOI：
10.1021/la5028724
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发表时间：
2014-12-09
期刊：
影响因子：
3.9
通讯作者：
Wang, Xuesong
中科院分区：
文献类型：
--
作者：
Li, Ke;Lei, Wanhua;Wang, Xuesong
合成了三种新型三芳基甲烷染料MPCV、DPCV和AEV，比较了它们对大肠杆菌和人肺癌A549细胞的光动力灭活能力，并与市售的两种TAMs进行了比较。MPCV和AEV亲水性的增强显著降低了它们对A549细胞的摄取。然而，它们与大肠杆菌细胞的结合亲和力与CV和EV相当，这是因为它们与高度负电荷的大肠杆菌外膜具有更好的静电吸引力。MPCV和AEV在照射后产生羟基自由基的效率也高于CV和EV。因此，与CV和EV相比，MPCV和AEV对大肠杆菌细胞的光动力灭活作用显著提高，而对A549细胞的光动力灭活作用显著减弱。由于DPCV在中性水溶液中具有较高的漂白倾向，其光动力灭活能力远低于CV。我们的工作表明，以适当的方式将可质子化基团引入TAMs的结构中，可能会导致对细菌细胞的选择性结合和光动力学失活。这一策略可以推广到其他类型的光动力抗菌化疗(PACT)药物，以提高其临床潜力。
Three new triarylmethane dyes (TAMs), MPCV, DPCV, and AEV, were synthesized and their photodynamic inactivation abilities against E. coli and human pulmonary carcinoma A549 cells were compared to two commercial TAMs, CV and EV. The enhanced hydrophilicity of MPCV and AEV decreases their cellular uptake to A549 cells dramatically. However, their binding affinity toward E. coli cells are comparable to that of CV and EV by virtue of the improved electrostatic attraction with highly negatively charged E. coli outer membranes. MPCV and AEV were also found to generate hydroxyl radicals more efficiently upon irradiation than CV and EV. Consequently, MPCV and AEV exhibited markedly improved photodynamic inactivation of E. coli cells but remarkably diminished photodynamic inactivation of A549 cells than CV and EV. The photodynamic inactivation ability of DPCV was much lower than that of CV due to its high propensity for bleaching in neutral aqueous solution. Our work demonstrates that the introduction of protonatable groups in a proper manner into the structures of TAMs may lead to selective binding and photodynamic inactivation toward bacterial cells over mammalian cells. This strategy may be extended to other types of photodynamic antimicrobial chemotherapy (PACT) agents to improve their clinical potential.