Yin Rui, Hamblin Michael R
Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom Street, Boston, MA 02114, United States.
Curr Med Chem. 2015;22(18):2159-85. doi: 10.2174/0929867322666150319120134.
Although photodynamic therapy (PDT) was discovered over a hundred years ago by its ability to destroy microorganisms, it has been developed mainly as a cancer therapy. In recent years, due to the inexorable rise in multi-antibiotic resistant strains of pathogens, PDT is being considered as a versatile antimicrobial approach to which microbial cells will not be able to develop resistance. The goal of this review is to survey the different classes of chemical compounds that have been tested as antimicrobial photosensitizers. Some of these compounds have been known for many years, while others have been rationally designed based on recently discovered structural principles. Tetrapyrrole-based compounds (some of which are approved as cancer therapies) that efficiently generate singlet oxygen are more efficient and broad-spectrum when they bear cationic charges, As the macrocycle structure moves from porphyrins to chlorins to phthalocyanines to bacteriochlorins the long wavelength absorption moves to the near-infrared where tissue penetration is better. Four main types of natural products have been tested: curcumin, riboflavin, hypericin and psoralens. Phenothiazinium dyes, such as methylene blue and toluidine blue, have been tested, and some are clinically approved. A variety of non-phenothiazinium dyes with xanthene, triarylmethane and indocyanine structures have also been tested. New ring structures based on BODIPY, squaraine and fullerene cages can also mediate antimicrobial PDT. Finally the process of photocatalysis using titanium dioxide can also have medical uses. Designing new antimicrobial photosensitizers is likely to keep chemists engaged for a long time to come.
尽管光动力疗法(PDT)在一百多年前就因其具有破坏微生物的能力而被发现,但它主要是作为一种癌症治疗方法发展起来的。近年来,由于多重耐药病原体菌株的不断增加,光动力疗法正被视为一种微生物细胞无法产生耐药性的通用抗菌方法。本综述的目的是调查已被测试作为抗菌光敏剂的不同类别的化合物。其中一些化合物已为人所知多年,而其他一些则是根据最近发现的结构原理进行合理设计的。基于四吡咯的化合物(其中一些已被批准用于癌症治疗)在带有阳离子电荷时能有效产生单线态氧,且效率更高、光谱更宽。随着大环结构从卟啉变为二氢卟酚、酞菁再到细菌叶绿素,长波长吸收向近红外移动,在近红外区域组织穿透性更好。已测试了四种主要类型的天然产物:姜黄素、核黄素、金丝桃素和补骨脂素。吩噻嗪鎓染料,如亚甲蓝和甲苯胺蓝,已被测试,其中一些已获得临床批准。还测试了多种具有呫吨、三芳基甲烷和吲哚菁结构的非吩噻嗪鎓染料。基于氟硼二吡咯、方酸菁和富勒烯笼的新环结构也可介导抗菌光动力疗法。最后,使用二氧化钛的光催化过程也可具有医学用途。设计新型抗菌光敏剂可能会使化学家在未来很长一段时间内都保持忙碌。