AIE-Armored Living Bacteriophage-DNA Bioconjugates for Targeting, Imaging, and Efficiently Elimination of Intracellular Bacterial Infection

Intracellular bacterial infections bring a considerable risk to human life and health due to their capacity to elude immune defenses and exhibit significant drug resistance. As a result, confronting and managing these infections presents substantial challenges. In this study, we developed a multifunctional phage bioconjugate by integrating aggregation-induced emission luminogen (AIEgen) photosensitizers and nucleic acid onto a bacteriophage framework (forming MS2-DNA-AIEgen bioconjugates). These bioconjugates can rapidly penetrate mammalian cells and specifically identify intracellular bacteria, while concurrently producing a detectable fluorescent signal. By harnessing the photodynamic properties of AIE photosensitizer and the bacteriophage's inherent lysis capability, the intracellular bacteria can be effectively eliminated and the functionality of the infected cells can be restored. In macrophage models infected with either antibiotic-sensitive or resistant Escherichia coli, MS2-DNA-AIEgen bioconjugates demonstrated excellent bacterial targeting and killing capability. Moreover, our engineered multifunctional phage bioconjugates were able to expedite the healing process in bacterially infected wounds observed in diabetic mice models while simultaneously enhancing immune activity within infected cells and in vivo, without displaying any noticeable toxicity. We envision that these innovative multifunctional phage bioconjugates, which utilize aggregation-induced luminescence photosensitizers and nucleic acids, may present a groundbreaking strategy for combating intracellular bacterial infections. This approach holds the potential to offer new avenues for future research and theranostic applications in the area of intracellular bacterial infections and associated diseases.