Aggregation-Induced Emission-Armored Living Bacteriophage-DNA Nanobioconjugates for Targeting, Imaging, and Efficient Elimination of Intracellular Bacterial Infection

Abstract

Intracellular bacterial infections bring a considerable risk to human life and health due to their capability to elude immune defenses and exhibit significant drug resistance. As a result, confronting and managing these infections present substantial challenges. In this study, we developed a multifunctional living phage nanoconjugate by integrating aggregationinduced emission luminogen (AIEgen) photosensitizers and nucleic acids onto a bacteriophage framework (forming MS2-DNA-AIEgen bioconjugates). These nanoconjugates can rapidly penetrate mammalian cells and specifically identify intracellular bacteria while concurrently producing a detectable fluorescent signal. By harnessing the photodynamic property of AIEgen photosensitizer and the bacteriophage's inherent targeting and lysis capability, the intracellular bacteria can be effectively eliminated and the activity of the infected cells can be restored. Moreover, our engineered phage nanoconjugates 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 noticeable toxicity. We envision that these multifunctional phage nanoconjugates, which utilize AIEgen photosensitizers and spherical nucleic acids, may present a groundbreaking strategy for combating intracellular bacteria and offer powerful avenues for theranostic applications in intracellular bacterial infection-associated diseases.

Photochemical Strategies toward Precision Targeting against Multidrug-Resistant Bacterial Infections

“…The biofilm was efficiently eliminated by 89.3% when the NB–bacteriophage complex concentration was elevated to 0.5 μM. The complex treatment healed A. baumannii -infected mouse skin quicker than ampicillin and polymyxin B. Zhang et al loaded AIEgen and nucleic acids onto a bacteriophage to from a nanoconjugate in order to combat intracellular bacteria . With the synergistic effect of PDT by AIEgen and targeting and lysis ability from bacteriophage, the intracellular E. coli can be thoroughly eliminated in vitro and in vivo .…”

All-in-One Alkaline Phosphatase-Response Aggregation-Induced Emission Probe for Cancer Discriminative Imaging and Combinational Chemodynamic–Photodynamic Therapy

“…However, the shortcomings of these imaging tools with high cost, hazardous ionizing radiation, and limited spatial resolution are becoming apparent and cannot be ignored. Alternatively, fluorescence (FL) imaging, with merits of high sensitivity and selectivity, fast response, a high signal-to-noise ratio, and noninvasiveness, is attracting growing interest in real-time visualization of biological processes at a molecular level. − Aggregation-induced emission luminogens (AIEgens), which are nonemissive or weak emissive in solution, can switch on intense FL after aggregation, giving a superior choice for high-quality FL imaging, with the inherent advantages of low background noise, strong photostability, a large Stokes shift, high brightness, and spatial resolution. , AIE probes have been precisely designed and widely applied for various biosensing and bioimaging in vitro and in vivo. − …”