Wu Xiaofeng, Yang Mengyao, Kim Ji Seon, Wang Rui, Kim Gyoungmi, Ha Jeongsun, Kim Heejeong, Cho Yejin, Nam Ki Taek, Yoon Juyoung
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03706, Republic of Korea.
Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul, 03760, Republic of Korea.
Angew Chem Int Ed Engl. 2022 Apr 19;61(17):e202200808. doi: 10.1002/anie.202200808. Epub 2022 Feb 28.
An effective strategy to engineer selective photodynamic agents to surmount bacterial-infected diseases, especially Gram-positive bacteria remains a great challenge. Herein, we developed two examples of compounds for a proof-of-concept study where reactive differences in reactive oxygen species (ROS) can induce selective ablation of Gram-positive bacteria. Sulfur-replaced phenoxazinium (NBS-N) mainly generates a superoxide anion radical capable of selectively killing Gram-positive bacteria, while selenium-substituted phenoxazinium (NBSe-N) has a higher generation of singlet oxygen that can kill both Gram-positive and Gram-negative bacteria. This difference was further evidenced by bacterial fluorescence imaging and morphological changes. Moreover, NBS-N can also successfully heal the Gram-positive bacteria-infected wounds in mice. We believe that such reactive differences may pave a general way to design selective photodynamic agents for ablating Gram-positive bacteria-infected diseases.
设计选择性光动力剂以克服细菌感染性疾病,尤其是革兰氏阳性菌感染,是一项极具挑战性的任务。在此,我们开发了两种化合物用于概念验证研究,其中活性氧(ROS)的反应性差异可诱导革兰氏阳性菌的选择性消融。硫取代的吩恶嗪鎓盐(NBS-N)主要产生能够选择性杀死革兰氏阳性菌的超氧阴离子自由基,而硒取代的吩恶嗪鎓盐(NBSe-N)则能产生更高水平的单线态氧,可杀死革兰氏阳性菌和革兰氏阴性菌。细菌荧光成像和形态变化进一步证明了这种差异。此外,NBS-N还能成功治愈小鼠体内革兰氏阳性菌感染的伤口。我们相信,这种反应性差异可能为设计用于消融革兰氏阳性菌感染性疾病的选择性光动力剂开辟一条通用途径。