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基于噬菌体导向的靶向、鉴别成像及 AIE 生物缀合物协同杀菌

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

机构信息

Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration and Reconstruction, Institute for Advanced Study, Division of Life Science, Department of Chemical and Biomedical Engineering , The Hong Kong University of Science and Technology , Clear Water Bay , Kowloon Hong Kong.

HKUST-Shenzhen Research Institute , Shenzhen 518057 , China.

出版信息

J Am Chem Soc. 2020 Feb 26;142(8):3959-3969. doi: 10.1021/jacs.9b12936. Epub 2020 Feb 14.

Abstract

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.

摘要

面对全球抗生素耐药性的危机,我们迫切需要具有特殊靶向特定细菌的能力和超强抗菌活性的新型药物。在此,我们提出了一种新策略,即用具有光动力失活(PDI)活性的聚集诱导发光(AIE)生色团(具有聚集诱导发射特性的发光体)来修饰噬菌体(PAP),以生成一种新型的 AIE-PAP 生物缀合物,该缀合物具有靶向成像和协同杀伤某些特定细菌的卓越能力。噬菌体赋予的靶向能力使生物缀合物能够特异性识别宿主细菌,同时保持噬菌体自身的感染活性。同时,AIE 特性使它们具有监测功能,因此可以通过方便的荧光成像实时跟踪它们与靶标的相互作用。更重要的是,PDI 活性的 AIE 生色团可以在白光照射下充当强大的原位光敏剂,产生高效的活性氧(ROS)。因此,在体外和体内抗菌试验中,该策略成功实现了对敏感抗生素和多药耐药(MDR)细菌的选择性靶向和协同杀伤,具有优异的生物相容性。这种新型的 AIE-噬菌体集成策略将丰富现有的抗菌药物库,并为未来开发有前途的药物候选物提供启示。

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