Ran Bei, Yuan Yuyu, Xia Wenxi, Li Mingle, Yao Qichao, Wang Zuokai, Wang Lili, Li Xiaoyu, Xu Yongping, Peng Xiaojun
State Key Laboratory of Fine Chemicals, Dalian University of Technology Dalian 116024 China
School of Bioengineering, Dalian University of Technology Dalian 116024 China.
Chem Sci. 2020 Nov 16;12(3):1054-1061. doi: 10.1039/d0sc04889e.
Antibiotic abuse causes the emergence of bacterial resistance. Photodynamic antibacterial chemotherapy (PACT) has great potential to solve serious bacterial resistance, but it suffers from the inefficient generation of ROS and the lack of bacterial targeting ability. Herein, a unique cationic photosensitizer (NB) and bacteriophage (ABP)-based photodynamic antimicrobial agent (APNB) is developed for precise bacterial eradication and efficient biofilm ablation. Thanks to the structural modification of the NB photosensitizer with a sulfur atom, it displays excellent reactive oxygen species (ROS)-production ability. Moreover, specific binding to pathogenic microorganisms can be provided by bacteriophages. The developed APNB has multiple functions, including bacteria targeting, near-infrared fluorescence imaging and combination therapy (PACT and phage therapy). Both and experiments prove that APNB can efficiently treat infection. Particularly, the recovery from infection after APNB treatment is faster than that with ampicillin and polymyxin B . Furthermore, the strategy of combining bacteriophages and photosensitizers is employed to eradicate bacterial biofilms for the first time, and it shows the excellent biofilm ablation effect as expected. Thus, APNB has huge potential in fighting against multidrug-resistant bacteria and biofilm ablation in practice.
抗生素滥用导致细菌耐药性的出现。光动力抗菌化疗（PACT）在解决严重的细菌耐药性方面具有巨大潜力，但它存在活性氧生成效率低下以及缺乏细菌靶向能力的问题。在此，开发了一种基于独特的阳离子光敏剂（NB）和噬菌体（ABP）的光动力抗菌剂（APNB），用于精确根除细菌和有效消除生物膜。由于NB光敏剂通过硫原子进行了结构修饰，它表现出优异的活性氧生成能力。此外，噬菌体能够实现与致病微生物的特异性结合。所开发的APNB具有多种功能，包括细菌靶向、近红外荧光成像以及联合治疗（PACT和噬菌体治疗）。体外和体内实验均证明APNB能够有效治疗感染。特别地，APNB治疗后从感染中恢复的速度比氨苄西林和多粘菌素B更快。此外，首次采用噬菌体和光敏剂相结合的策略来根除细菌生物膜，并且如预期所示，它显示出优异的生物膜消除效果。因此，APNB在实际对抗多重耐药细菌和生物膜消除方面具有巨大潜力。
