Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 142, Issue 8, Pages 3959-3969Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.9b12936
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Funding
- Research Grants Council of Hong Kong [C6009-17G]
- Innovation and Technology Commission [ITC-CNERC14SC01]
- National Natural Science Foundation of China [21705111, 21788102, 81672112, 81972025]
- Natural Science Foundation of Guangdong Province [2019B030301003]
- National Key Research and Development program of China [2018YFE0190200]
- Science and Technology Plan of Shenzhen [JCYJ20180507183832744, JCYJ20160229205601482]
- Chongqing Technology Innovation and Application Demonstration Project [cstc2018jscx-msybX0010]
- Chongqing Special Postdoctoral Science Foundation [Xm2017090]
- Science and Technology Research Program of Chongqing Municipal Education Commission [Kjqn201900416]
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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.
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