CQC-IMS, Chemistry Department, University of Coimbra, Coimbra 3004-535, Portugal.
Łukasiewicz Research Network - Kraków Institute of Technology, Kraków 30-418, Poland.
ACS Infect Dis. 2024 Sep 13;10(9):3368-3377. doi: 10.1021/acsinfecdis.4c00492. Epub 2024 Aug 16.
Various cationic photosensitizers employed in antimicrobial photodynamic therapy (aPDT) have the ability to photoinactivate planktonic bacteria under conditions of low phototoxicity to mammalian cells and without generating antimicrobial resistance (AMR). However, the photoinactivation of biofilms requires orders-of-magnitude higher photosensitizer concentrations, which become toxic to host cells. Remarkably, the bactericidal effect of a dicationic di-imidazolyl chlorin toward planktonic and was observed in this work for concentrations below 400 nM under illumination at 660 nm and below 50 μM for the corresponding biofilms. At the latter concentrations, the chlorin is phototoxic toward human keratinocyte cells. However, in the presence of 50 mM KI, bactericidal concentrations are reduced to less than 50 nM for planktonic bacteria and to less than 1 μM for biofilms. It is shown that the potentiation with KI involves the triiodide anion. This potentiation elicits a bactericidal effect without appreciable cytotoxicity to keratinocytes. It becomes possible to selectively inactivate biofilms with aPDT. An exploratory study treating mice with wounds infected with expressing GFP with 20 μM chlorin and 120 J cm at 652 nm confirmed the potential of this chlorin to control localized infections.
各种阳离子光动力抗菌治疗（aPDT）中使用的光敏剂在低细胞毒性和不产生抗微生物耐药性（AMR）的条件下具有光灭活浮游细菌的能力。然而，生物膜的光灭活需要数量级更高的光敏剂浓度，这对宿主细胞是有毒的。值得注意的是，在 660nm 光照下，浓度低于 400nM 时，二价二咪唑基氯对浮游菌和的杀菌作用在这项工作中得到了观察，而相应的生物膜的浓度则低于 50μM。在后一种浓度下，该氯对人角质形成细胞具有光毒性。然而，在 50mM KI 的存在下，杀菌浓度对于浮游菌降低至低于 50nM，对于生物膜降低至低于 1μM。结果表明，KI 的增效作用涉及三碘化物阴离子。这种增效作用在没有明显细胞毒性的情况下引发杀菌作用。可以用 aPDT 选择性地灭活生物膜。一项用表达 GFP 的 感染的小鼠进行的探索性研究，用 20μM 氯和 652nm 处的 120J cm 处理，证实了这种氯控制局部感染的潜力。
