Aggregation-Induced Emission-Armored Living Bacteriophage-DNA Nanobioconjugates for Targeting, Imaging, and Efficient Elimination of Intracellular Bacterial Infection
Jing Zhang1, Xuewen He1*（何学文）,Ben Zhong Tang2*（唐本忠）
1The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren’ai Road, Suzhou 215123, China
2School of Science and Engineering,ShenzhenInstitute of AggregateScience and Technology,TheChinese Universityof Hong Kong, Shenzhen(CUHK−Shenzhen),Guangdong,518172,China
ACS Nano 2024, 18, 4, 3199–3213
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 aggregation-induced 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.
链接：https://pubs.acs.org/doi/10.1021/acsnano.3c09695
