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

被引:193
作者
He, Xuewen [3 ,4 ]
Yang, Yujun [1 ,2 ]
Guo, Yongcan [6 ]
Lu, Shuguang [7 ]
Du, Yao [1 ,2 ]
Li, Jun-Jie [1 ,2 ]
Zhang, Xuepeng [3 ,4 ]
Leung, Nelson L. C. [3 ,4 ]
Zhao, Zheng [3 ,4 ]
Niu, Guangle [3 ,4 ]
Yang, Shuangshuang [1 ,2 ]
Weng, Zhi [1 ,2 ]
Kwok, Ryan T. K. [3 ,4 ]
Lam, Jacky W. Y. [3 ,4 ]
Xie, Guoming [1 ,2 ]
Tang, Ben Zhong [3 ,4 ,5 ]
机构
[1] Chongqing Med Univ, Chongqing Med Lab Microfluid, Dept Lab Med, Key Lab Lab Med Diagnost,Minist Educ, Chongqing 400016, Peoples R China
[2] Chongqing Med Univ, SPRi Engn Res Ctr, Chongqing 400016, Peoples R China
[3] Hong Kong Univ Sci & Technol, Dept Chem & Biomed Engn, Div Life Sci,Kowloon,Inst Adv Study, Dept Chem,Hong Kong Branch,Chinese Natl Engn Res, Clear Water Bay, Hong Kong, Peoples R China
[4] HKUST Shenzhen Res Inst, Shenzhen 518057, Peoples R China
[5] South China Univ Technol, State Key Lab Luminescent Mat & Devices, SCUT HKUST Joint Res Lab, NSFC Ctr Luminescence Mol Aggregates, Guangzhou 510640, Peoples R China
[6] Southwest Med Univ, Tradit Chinese Med Hosp, Clin Lab, Luzhou 646000, Peoples R China
[7] Army Med Univ, Coll Basic Med Sci, Dept Microbiol, Chongqing 400038, Peoples R China
基金
中国国家自然科学基金;
关键词
AGGREGATION-INDUCED EMISSION; GUT MICROBIOTA; CANCER; RESISTANCE; INFECTION; THERAPY; CELLS; MODEL;
D O I
10.1021/jacs.9b12936
中图分类号
O6 [化学];
学科分类号
0703 ;
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 AlEgens 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.
引用
收藏
页码:3959 / 3969
页数:11
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