Engineering Bacteriophage Cocktail with Mutually Promoted Chemodynamic-Photodynamic Activity for Targeted and Synergistic Biofilm Eradication
Jing Zhang1, Ling-Hong Xiong2, Ben Zhong Tang3,4, Xuewen He(何学文)1*
1State Key Laboratory of Bioinspired Interfacial Materials Science, The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
2School of Public Health, Suzhou Medical College of Soochow University, Soochow University, Suzhou 215123, China
3Guangdong Basic Research Center of Excellence for Aggregate Science, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China
4Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration and Reconstruction, Institute for Advanced Study and Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon 00852 Hong Kong, China
ACS Nano2026, 20, 6063–6080
Abstract: Biofilms formed by bacterial symbiosis significantly strengthen bacterial resistance to external interference and cause chronic infections. Herein, a chemodynamic therapy (CDT) and photodynamic therapy (PDT) coarmed bacteriophage cocktail was developed to eradicate Staphylococcus aureus biofilms by conjugating aggregation-induced emission photosensitizer (AIE PSs), glucose oxidase (GOx), and horseradish peroxidase (HRP) on the bacteriophage surface. Leveraging the particular specificity of the bacteriophage toward host bacteria, the three conjugates can penetrate the biofilm and colocalize on the inner bacterial surface. When thus enriched, AIE PSs exhibited intensified fluorescence, enabling labeling and killing pathogens via photoirradiation-generated singlet oxygen. After combining AIE PSs with GOx/HRP, which can convert glucose nutrients into H2O2 and ultimately to hydroxyl radicals via cascade catalysis, the bactericidal efficiency was dramatically improved compared to individual phage-CDT (>468%) or phage-PDT (>290%) at the same PFU concentration of phage. The colocalized PSs and enzymes on the confined space of the bacterial surface are mutually promoted in the microenvironment of the biofilm, realizing synergistic enhancement. This strengthened bacteriophage cocktail offers an effective strategy for treating biofilm-related clinical superbug infections.
Article information: https://doi.org/10.1021/acsnano.5c19780