Phage-Guided Targeting, Discriminative Imaging, and Synergistic Killing of Bacteria by AIE Bioconjugates.
Xuewen HeYujun YangYongcan GuoShuguang LuYao DuJun-Jie LiXuepeng ZhangNelson L C LeungZheng ZhaoGuangle NiuShuangshuang YangZhi WengRyan Tsz Kin KwokJacky W Y LamGuoming XieBen-Zhong TangPublished in: Journal of the American Chemical Society (2020)
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.
Keyphrases
- cancer therapy
- drug resistant
- fluorescence imaging
- drug delivery
- reactive oxygen species
- multidrug resistant
- high efficiency
- fluorescent probe
- pseudomonas aeruginosa
- living cells
- high resolution
- photodynamic therapy
- silver nanoparticles
- public health
- cell death
- dna damage
- current status
- emergency department
- oxidative stress
- mass spectrometry
- anti inflammatory
- genetic diversity
- structural basis
- adverse drug