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

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 realtime 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.

Gathering brings strength: How organic aggregates boost disease phototheranostics

“…AIEgens have been used in many areas including optoelectronic devices, process and environment monitoring, chemical sensing, and biological imaging 58–65 . Thanks to the intrinsic merits of large Stokes shift, high brightness, good stability and biocompatibility, and turn‐on property from solution to aggregate, AIEgens have also shown great promise in the field of biomedical applications 66–73 …”

Aggregation‐Induced Emission: A Rising Star in Chemistry and Materials Science

“…[ 47 ] This strategy opens up a new avenue for the in vivo labeling and detection or monitoring applications of AIEgens. [ 48 ] With the intensive attention of RTP materials in recent years, the biological applications of AIEgens with bright persistent RTP were also explored in 2017 by Liu and Chi et al . [ 49 ] Furthermore, the elegant design of AIE photosensitizers and AIEgens with prominent photothermal effect further expanded AIE applications to theranostic probes.…”

A Pseudopaline Fluorescent Probe for the Selective Detection of Pseudomonas aeruginosa

“…To address this issue, effective bacterial imaging is an emerging strategy that could diagnose bacterial infections in a matter of hours. [9][10][11] Several types of chemical probes such as fluorescent derivatives of antibiotics or antimicrobial peptides, [12][13][14][15][16][17][18][19][20][21][22][23] nitroreductase-triggered probes, 24,25 glycoprotein-targeted probes, 26 siderophore-based probes, [27][28][29][30] maltodextrin-based probes, 31 and probes with aggregation-induced emission property (AIEgen) [32][33][34][35][36] have been reported. Near-infrared (NIR) dyes could replace the fluorescent part of these probes for live imaging to detect deep tissue infections inaccessible by the conventional sampling method.…”