Hollow Mesoporous Molybdenum Single-Atom Nanozyme-Based Reactor for Enhanced Cascade Catalytic Antibacterial Therapy

Purpose: The remarkable peroxidase-like activity of single-atom nanozymes (SAzymes) allows them to catalyze the conversion of H₂O₂ to •OH, rendering them highly promising for antibacterial applications. However, their practical in vivo application is hindered by the near-neutral pH and insufficient H₂O₂ levels present in physiological systems. This study was aimed at developing a SAzyme-based nanoreactor and investigating its in vivo antibacterial activity.

Methods: We developed a hollow mesoporous molybdenum single-atom nanozyme (HMMo-SAzyme) using a controlled chemical etching approach and pyrolysis strategy. The HMMo-SAzyme not only exhibited excellent catalytic activity but also served as an effective nanocarrier. By loading glucose oxidase (GOx) with HMMo-SAzyme and encapsulating it with hyaluronic acid (HA), a nanoreactor (HMMo/GOx@HA) was constructed as glucose-triggered cascade catalyst for combating bacterial infection in vivo.

Results: Hyaluronidase (HAase) at the site of infection degraded HA, allowing GOx to convert glucose into gluconic acid and H₂O₂. An acid environment significantly enhanced the catalytic activity of HMMo-SAzyme to promote the further catalytic conversion of H₂O₂ to •OH for bacterial elimination. In vitro and in vivo experiments demonstrated that the nanoreactor had excellent antibacterial activity and negligible biological toxicity.

Conclusion: This study represents a significant advancement in developing a cascade catalytic system with high efficiency based on hollow mesoporous SAzyme, promising the advancement of biological applications of SAzyme.