Microenvironment‐Activated Nanozyme‐Armed Bacteriophages Efficiently Combat Bacterial Infection

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.