Phage-Guided Targeting, Discriminative Imaging, and Synergistic Killing of Bacteria by AIE Bioconjugates

化学 细菌 生物结合 噬菌体 致病菌 组合化学 纳米技术 大肠杆菌 生物化学 遗传学 生物 基因 材料科学
作者
Xuewen He,Yujun Yang,Yongcan Guo,Shuguang Lu,Yao Du,Junjie Li,Xuepeng Zhang,Nelson L. C. Leung,Zheng Zhao,Guangle Niu,Shuangshuang Yang,Zhi Weng,Ryan T. K. Kwok,Jacky W. Y. Lam,Guoming Xie,Ben Zhong Tang
出处
期刊:Journal of the American Chemical Society [American Chemical Society]
卷期号:142 (8): 3959-3969 被引量:172
标识
DOI:10.1021/jacs.9b12936
摘要

New agents with particular specificity toward targeted bacteria and superefficacy in antibacterial activity are urgently needed in facing the crisis of worldwide antibiotic resistance. Herein, a novel strategy by equipping bacteriophage (PAP) with photodynamic inactivation (PDI)-active AIEgens (luminogens with aggregation-induced emission property) was presented to generate a type of AIE–PAP bioconjugate with superior capability for both targeted imaging and synergistic killing of certain species of bacteria. The targeting ability inherited from the bacteriophage enabled the bioconjugates to specifically recognize the host bacteria with preserved infection activity of phage itself. Meanwhile, the AIE characteristic empowered them a monitoring functionality, and the real-time tracking of their interactions with targets was therefore realized via convenient fluorescence imaging. More importantly, the PDI-active AIEgens could serve as powerful in situ photosensitizers producing high-efficiency reactive oxygen species (ROS) under white light irradiation. As a result, selective targeting and synergistic killing of both antibiotic-sensitive and multi-drug-resistant (MDR) bacteria were successfully achieved in in vitro and in vivo antibacterial tests with excellent biocompatibility. This novel AIE–phage integrated strategy would diversify the existing pool of antibacterial agents and inspire the development of promising drug candidates in the future.
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