Microenvironment‐Activated Nanozyme‐Armed Bacteriophages Efficiently Combat Bacterial Infection

Abstract

Bacterial infection is one of the greatest challenges to public health, requiring new therapeutic methods. Herein, an innovative nanozyme‐armed phage (phage@palladium (Pd)) system is fabricated for combating bacterial infection. The proposed phage@Pd preserves the function of the phages to achieve precise recognition and adhesion to the host Escherichia coli. In aid of the phages, the ultrasmall Pd nanozymes equipped with conspicuous pH‐dependent peroxidase‐like activity can generate toxic hydroxyl radical around the bacteria in acidic and hydrogen‐peroxide‐overexpressed infection microenvironment while remaining inert in physiological conditions, thus realizing the noteworthy elimination of bacteria at infected sites, and in the meantime ensuring the biological safety of phage@Pd in healthy tissues. In addition, the filamentous structure of phage@Pd can also enhance its bactericidal efficiency toward nonhost bacteria by randomly entangling on them, indicating possible broad‐spectrum germicidal efficacy. Notably, phage@Pd can not only eradicate planktonic bacteria, but also kill the bacteria inside the biofilm in vitro. For both in vivo models of acute bacterial pneumonia or subcutaneous abscess, phage@Pd shows significant activity in eliminating infection and promoting tissue recovery. These results demonstrate that the phage@Pd nanohybrid is a safe and effective antimicrobial agent, providing a new insight into development of advanced antibacterial materials.

A Comparative Analysis of the Antibacterial Spectrum of Ultrasmall Manganese Ferrite Nanozymes with Varied Surface Modifications

“…Moreover, bacteria have the ability to form biofilms, acting as both physical and chemical barriers around infections. This significantly enhances antibiotic tolerance by several orders of magnitude. , Hence, it is imperative to develop new antimicrobial approaches, and extensive interdisciplinary endeavors have been undertaken to explore and design novel and more efficient antimicrobial agents. The swift advancements in nanozymes offer us novel avenues to address these issues.…”

Advanced nanozymes possess peroxidase-like catalytic activities in biomedical and antibacterial fields: review and progress

“…Jin et al combined the M13 phage with the PEGylated Pt nanozyme through amide reactions to form a phage@Pt nano-platform for selective targeting. 98 This mechanism is attributed to the phage's ability to target and firmly bind to host bacteria ( e.g. , E. coli ), while for non-host bacteria, the linear structure of the phage can also play a role in entanglement.…”

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

“…Prompted by the growing crisis in antibiotic resistance, phage therapy is experiencing a resurgence as a potent solution against bacterial infections . Nonetheless, conventional phage therapies often face limitations due to their modest antibacterial properties and struggles in adverse microenvironments, resulting in reduced antibacterial efficacy in real-world infectionsparticularly in acute cases and specific severe infectious diseases, such as those affecting immunocompromised diabetic patients. , Although it has been reported to promote the bactericidal activity of native phages by modifying with a few functional molecules and nanomaterials, − the application of phages for intracellular bacterial labeling, imaging, and killing has not yet been reported.…”