A Glucose-Powered Activatable Nanozyme Breaking pH and H₂ O₂ Limitations for Treating Diabetic Infections

The peroxidase-like activity of nanozymes is promising for chemodynamic therapy by catalyzing H₂ O₂ into ^. OH. However, for most nanozymes, this activity is optimal just in acidic solutions, while the pH of most physiological systems is beyond 7.0 (even >8.0 in chronic wounds) with inadequate H₂ O₂ . We herein communicate an activatable nanozyme with targeting capability to simultaneously break the local pH and H₂ O₂ limitations under physiological conditions. As a proof of concept, aptamer-functionalized nanozymes, glucose oxidase, and hyaluronic acid constitute an activatable nanocapsule "APGH", which can be activated by bacteria-secreted hyaluronidase in infected wounds. Nanozymes bind onto bacteria through aptamer recognition, and glucose oxidation tunes the local pH down and supplements H₂ O₂ for the in-situ generation of ^. OH on bacteria surfaces. The activity switching and enhanced antibacterial effect of the nanocapsule were verified in vitro and in diabetic wounds. This strategy for directly regulating local microenvironment is generally accessible for nanozymes, and significant for facilitating biological applications of nanozymes.